rs17291650

chr12-50819650-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005171.5(ATF1):c.687A>G(p.Glu229=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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]

ACMG classification

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/exons	MANE	UniProt
ATF1	NM_005171.5	c.687A>G	p.Glu229=	synonymous_variant	7/7	ENST00000262053.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF1	ENST00000262053.8	c.687A>G	p.Glu229=	synonymous_variant	7/7	1	NM_005171.5	P1
ATF1	ENST00000551831.5	c.*284A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9649 AN: 152156 Hom.: 437 Cov.: 32

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

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.: 31 AF XY: 0.0856 AC XY: 62157 AN XY: 726014

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.: 32 AF XY: 0.0600 AC XY: 4470 AN XY: 74450

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

Other links and lift over

dbSNP: rs17291650; hg19: chr12-51213433;