dbSNP rs17291650: ATF1:p.Glu229Glu (chr12-50819650-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005171.5(ATF1):c.687A>G(p.Glu229Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,612,082 control chromosomes in the GnomAD database, including 6,390 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 437 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5953 hom. )

Consequence

ATF1
NM_005171.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

23 publications found

Variant links:

Genes affected

ATF1 (HGNC:783): (activating transcription factor 1) This gene encodes an activating transcription factor, which belongs to the ATF subfamily and bZIP (basic-region leucine zipper) family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. This protein is phosphorylated at serine 63 in its kinase-inducible domain by serine/threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I/II, mitogen- and stress-activated protein kinase and cyclin-dependent kinase 3 (cdk-3). Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in angiomatoid fibrous histiocytoma and clear cell sarcoma. This gene has a pseudogene on chromosome 6. [provided by RefSeq, Aug 2010]

ATF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.647 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF1	NM_005171.5 link	c.687A>G	p.Glu229Glu	synonymous_variant	Exon 7 of 7	ENST00000262053.8	NP_005162.1	P18846-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATF1	ENST00000262053.8 link	c.687A>G	p.Glu229Glu	synonymous_variant	Exon 7 of 7	1	NM_005171.5	ENSP00000262053.3	P18846-1
ATF1	ENST00000551831.5 link	n.*284A>G		non_coding_transcript_exon_variant	Exon 6 of 6	2		ENSP00000448987.1	F8VYE5
ATF1	ENST00000551831.5 link	n.*284A>G		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000448987.1	F8VYE5

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9649

AN:

152156

Hom.:

437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0950

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0621

Gnomad FIN

AF:

0.0559

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0602

GnomAD2 exomes

AF:

0.0672

AC:

16744

AN:

249302

AF XY:

0.0693

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.0314

Gnomad ASJ exome

AF:

0.0941

Gnomad EAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0956

Gnomad OTH exome

AF:

0.0706

GnomAD4 exome

AF:

0.0859

AC:

125367

AN:

1459808

Hom.:

5953

Cov.:

AF XY:

0.0856

AC XY:

62157

AN XY:

726014

show subpopulations

African (AFR)

AF:

0.0123

AC:

410

AN:

33430

American (AMR)

AF:

0.0332

AC:

1476

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.0953

AC:

2488

AN:

26100

East Asian (EAS)

AF:

0.000302

AC:

AN:

39670

South Asian (SAS)

AF:

0.0692

AC:

5920

AN:

85516

European-Finnish (FIN)

AF:

0.0614

AC:

3280

AN:

53396

Middle Eastern (MID)

AF:

0.0650

AC:

371

AN:

5708

European-Non Finnish (NFE)

AF:

0.0962

AC:

106872

AN:

1111126

Other (OTH)

AF:

0.0752

AC:

4538

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

5660

11321

16981

22642

28302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3758

7516

11274

15032

18790

<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:

0.0633

AC:

9646

AN:

152274

Hom.:

437

Cov.:

AF XY:

0.0600

AC XY:

4470

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0153

AC:

638

AN:

41574

American (AMR)

AF:

0.0468

AC:

716

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0950

AC:

330

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5194

South Asian (SAS)

AF:

0.0620

AC:

299

AN:

4826

European-Finnish (FIN)

AF:

0.0559

AC:

592

AN:

10598

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6808

AN:

68000

Other (OTH)

AF:

0.0595

AC:

126

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

449

898

1348

1797

2246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0838

Hom.:

2371

Bravo

AF:

0.0585

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

EpiCase

AF:

0.0903

EpiControl

AF:

0.0907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.9

(source)

DANN

Benign

0.52

PhyloP100

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

Other links and lift over