Genetic Variant NM_005171.5:c.687A>G (chr12-50819650-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.0672

AC:

16744

AN:

249302

Hom.:

710

AF XY:

0.0693

AC XY:

9330

AN XY:

134678

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 SAS exome

AF:

0.0678

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

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.0332

Gnomad4 ASJ exome

AF:

0.0953

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0692

Gnomad4 FIN exome

AF:

0.0614

Gnomad4 NFE exome

AF:

0.0962

Gnomad4 OTH exome

AF:

0.0752

GnomAD4 genome

AF:

0.0633

AC:

9646

AN:

152274

Hom.:

437

Cov.:

AF XY:

0.0600

AC XY:

4470

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.0468

Gnomad4 ASJ

AF:

0.0950

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0620

Gnomad4 FIN

AF:

0.0559

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0595

Alfa

AF:

0.0881

Hom.:

1690

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

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over