Variant rs3213764 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
ATF7IP	NM_018179.5 linkuse as main transcript	c.1589A>G	p.Lys530Arg	missense_variant	3/15	ENST00000261168.9	NP_060649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF7IP	ENST00000261168.9 linkuse as main transcript	c.1589A>G	p.Lys530Arg	missense_variant	3/15	5	NM_018179.5	ENSP00000261168	P5	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

GnomAD3 exomes

AF:

0.465

AC:

113212

AN:

243266

Hom.:

27272

AF XY:

0.471

AC XY:

61932

AN XY:

131614

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 SAS exome

AF:

0.434

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

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.427

AC:

65003

AN:

152082

Hom.:

14742

Cov.:

AF XY:

0.434

AC XY:

32229

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.598

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.481

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.469

Hom.:

35342

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2020	This variant is associated with the following publications: (PMID: 23359319) -

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

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

MutationTaster

Benign

0.027

P;P;P;P;P

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

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over