Genetic Variant ATF1:c.-7+339G>T (chr12-50764080-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001412963.1(ATF1):c.-7+339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 143,632 control chromosomes in the GnomAD database, including 9,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 9019 hom., cov: 25)

Exomes 𝑓: 0.31 ( 0 hom. )

Consequence

ATF1
NM_001412963.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.256

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-50764080-G-T is Benign according to our data. Variant chr12-50764080-G-T is described in ClinVar as [Benign]. Clinvar id is 1224709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF1	NM_005171.5 link	c.-234G>T		upstream_gene_variant		ENST00000262053.8	NP_005162.1	P18846-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATF1	ENST00000552510.5 link	c.-7+339G>T	intron_variant	Intron 1 of 4	5		ENSP00000448592.1	F8VS03
ATF1	ENST00000549612.5 link	n.-234G>T	non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000448421.1	F8VRN2
ATF1	ENST00000549612.5 link	n.-234G>T	5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000448421.1	F8VRN2
ATF1	ENST00000262053.8 link	c.-234G>T	upstream_gene_variant		1	NM_005171.5	ENSP00000262053.3	P18846-1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

51412

AN:

143528

Hom.:

9023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.349

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.313

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.358

AC:

51412

AN:

143616

Hom.:

9019

Cov.:

AF XY:

0.355

AC XY:

24706

AN XY:

69590

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.364

Hom.:

2113

Bravo

AF:

0.344

Asia WGS

AF:

0.323

AC:

1098

AN:

3400

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31204011) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.70

Splicing

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