12-14434367-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018179.5(ATF7IP):c.1589A>G(p.Lys530Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,571,092 control chromosomes in the GnomAD database, including 170,778 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14742 hom., cov: 33)

Exomes 𝑓: 0.46 ( 156036 hom. )

Consequence

ATF7IP
NM_018179.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.11

Publications

62 publications found

Variant links:

Genes affected

ATF7IP (HGNC:20092): (activating transcription factor 7 interacting protein) ATF7IP is a multifunctional nuclear protein that associates with heterochromatin. It can act as a transcriptional coactivator or corepressor depending upon its binding partners (summary by Liu et al., 2009 [PubMed 19106100]).[supplied by OMIM, Nov 2010]

ATF7IP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3941526E-4).

BP6

Variant 12-14434367-A-G is Benign according to our data. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-14434367-A-G is described in CliVar as Benign. Clinvar id is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF7IP	NM_018179.5 link	c.1589A>G	p.Lys530Arg	missense_variant	Exon 3 of 15	ENST00000261168.9	NP_060649.3	Q6VMQ6-1A0A024RAY1B3KNI7B3KQF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF7IP	ENST00000261168.9 link	c.1589A>G	p.Lys530Arg	missense_variant	Exon 3 of 15	5	NM_018179.5	ENSP00000261168.4		Q6VMQ6-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64993

AN:

151964

Hom.:

14741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.434

GnomAD2 exomes

AF:

0.465

AC:

113212

AN:

243266

AF XY:

0.471

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.463

AC:

657043

AN:

1419010

Hom.:

156036

Cov.:

AF XY:

0.465

AC XY:

328899

AN XY:

707682

show subpopulations

African (AFR)

AF:

0.258

AC:

8425

AN:

32622

American (AMR)

AF:

0.377

AC:

16214

AN:

43040

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

13376

AN:

25726

East Asian (EAS)

AF:

0.618

AC:

23950

AN:

38742

South Asian (SAS)

AF:

0.444

AC:

37190

AN:

83722

European-Finnish (FIN)

AF:

0.593

AC:

31616

AN:

53288

Middle Eastern (MID)

AF:

0.454

AC:

2565

AN:

5646

European-Non Finnish (NFE)

AF:

0.461

AC:

496812

AN:

1077294

Other (OTH)

AF:

0.456

AC:

26895

AN:

58930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

14973

29946

44919

59892

74865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14446

28892

43338

57784

72230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

65003

AN:

152082

Hom.:

14742

Cov.:

AF XY:

0.434

AC XY:

32229

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.280

AC:

11622

AN:

41506

American (AMR)

AF:

0.378

AC:

5768

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1877

AN:

3468

East Asian (EAS)

AF:

0.598

AC:

3095

AN:

5178

South Asian (SAS)

AF:

0.446

AC:

2152

AN:

4828

European-Finnish (FIN)

AF:

0.606

AC:

6387

AN:

10540

Middle Eastern (MID)

AF:

0.411

AC:

120

AN:

292

European-Non Finnish (NFE)

AF:

0.481

AC:

32666

AN:

67974

Other (OTH)

AF:

0.436

AC:

920

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1827

3654

5480

7307

9134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.464

Hom.:

75294

Bravo

AF:

0.402

TwinsUK

AF:

0.458

AC:

1697

ALSPAC

AF:

0.470

AC:

1813

ESP6500AA

AF:

0.297

AC:

1310

ESP6500EA

AF:

0.487

AC:

4184

ExAC

AF:

0.471

AC:

57130

Asia WGS

AF:

0.461

AC:

1601

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 28, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23359319) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;.;.;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.59

T;T;T;T;.

MetaRNN

Benign

0.00014

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;.;.;.;L

PhyloP100

2.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.62

N;N;N;N;N

REVEL

Benign

0.049

Sift

Uncertain

0.020

D;T;D;D;D

Sift4G

Uncertain

0.056

T;T;D;T;T

Polyphen

0.97

D;D;.;.;D

Vest4

0.057

MPC

0.31

ClinPred

0.014

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.024

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over