12-50764080-G-T

Position:

• chr12-50764080-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.256

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 -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/exons	MANE	Protein	UniProt
ATF1	NM_005171.5	c.-234G>T		upstream_gene_variant		ENST00000262053.8	NP_005162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF1	ENST00000552510.5	c.-7+339G>T		intron_variant		5		ENSP00000448592.1
ATF1	ENST00000549612.5	n.-234G>T		non_coding_transcript_exon_variant	1/5	5		ENSP00000448421.1
ATF1	ENST00000549612.5	n.-234G>T		5_prime_UTR_variant	1/5	5		ENSP00000448421.1
ATF1	ENST00000262053.8	c.-234G>T		upstream_gene_variant		1	NM_005171.5	ENSP00000262053.3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 51412 AN: 143528 Hom.: 9023 Cov.: 25

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: 5 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.358 AC: 51412 AN: 143616 Hom.: 9019 Cov.: 25 AF XY: 0.355 AC XY: 24706 AN XY: 69590

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

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	Feb 17, 2020	This variant is associated with the following publications: (PMID: 31204011) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61926301; hg19: chr12-51157863;