12-50809588-C-T

Position:

chr12-50809588-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

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:

ATF1 (HGNC:):

ATF1 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/7	ENST00000262053.8	NP_005162.1	P18846-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATF1	ENST00000262053.8 linkuse as main transcript	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/7	1	NM_005171.5	ENSP00000262053.3	P18846-1
ATF1	ENST00000552487.1 linkuse as main transcript	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/6	5		ENSP00000448921.1	F8VYN3
ATF1	ENST00000552510.5 linkuse as main transcript	c.327C>T	p.Tyr109Tyr	splice_region_variant, synonymous_variant	4/5	5		ENSP00000448592.1	F8VS03
ATF1	ENST00000551831.5 linkuse as main transcript	n.94-4422C>T		intron_variant		2		ENSP00000448987.1	F8VYE5

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61769

AN:

151332

Hom.:

13289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.386

AC XY:

279889

AN XY:

724926

show subpopulations

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.:

AF XY:

0.400

AC XY:

29613

AN XY:

73968

show subpopulations

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

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	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

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

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