chr12-50809588-C-T

Position:

• chr12-50809588-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000262053.8(ATF1):​c.327C>T​(p.Tyr109Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,608,190 control chromosomes in the GnomAD database, including 124,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13308 hom., cov: 31)
  • Exomes 𝑓: 0.39 (111542 hom.)
• Consequence: ATF1 ENST00000262053.8 splice_region, synonymous
• Scores: Splicing: ADA: 0.004790
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.01

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 12-50809588-C-T is Benign according to our data. Variant chr12-50809588-C-T is described in ClinVar as [Benign]. Clinvar id is 1285794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF1	NM_005171.5	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/7	ENST00000262053.8	NP_005162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF1	ENST00000262053.8	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/7	1	NM_005171.5	ENSP00000262053.3
ATF1	ENST00000552487.1	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/6	5		ENSP00000448921.1
ATF1	ENST00000552510.5	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/5	5		ENSP00000448592.1
ATF1	ENST00000551831.5	n.94-4422C>T		intron_variant		2		ENSP00000448987.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61769 AN: 151332 Hom.: 13289 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.410

GnomAD3 exomes AF: 0.353 AC: 88402 AN: 250102 Hom.: 16543 AF XY: 0.356 AC XY: 48122 AN XY: 135226

Gnomad AFR exome AF: 0.543

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.387 AC: 563475 AN: 1456742 Hom.: 111542 Cov.: 37 AF XY: 0.386 AC XY: 279889 AN XY: 724926

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.408 AC: 61818 AN: 151448 Hom.: 13308 Cov.: 31 AF XY: 0.400 AC XY: 29613 AN XY: 73968

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.408

Alfa AF: 0.385 Hom.: 21704

Bravo AF: 0.413

Asia WGS AF: 0.351 AC: 1221 AN: 3478

EpiCase AF: 0.386

EpiControl AF: 0.394

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29547645, 26553438) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0048
dbscSNV1_RF	Benign	0.084
SpliceAI score (max)		0.030		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: rs1129406; hg19: chr12-51203371; COSMIC: COSV50395907; COSMIC: COSV50395907;