NM_005171.5:c.-6-4815T>G

Variant names:

• chr12-50775325-T-G
• rs7959129
• NM_005171.5:c.-6-4815T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005171.5(ATF1):​c.-6-4815T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,270 control chromosomes in the GnomAD database, including 55,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (55413 hom., cov: 30)
• Consequence: ATF1 NM_005171.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0870

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 12-50775325-T-G is Benign according to our data. Variant chr12-50775325-T-G is described in ClinVar as [Benign]. Clinvar id is 1259273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF1	NM_005171.5	c.-6-4815T>G		intron_variant	Intron 1 of 6	ENST00000262053.8	NP_005162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF1	ENST00000262053.8	c.-6-4815T>G		intron_variant	Intron 1 of 6	1	NM_005171.5	ENSP00000262053.3

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127185 AN: 151156 Hom.: 55403 Cov.: 30

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.872

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.841 AC: 127228 AN: 151270 Hom.: 55413 Cov.: 30 AF XY: 0.839 AC XY: 62055 AN XY: 73976

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.977

Gnomad4 OTH AF: 0.873

Alfa AF: 0.941 Hom.: 21086

Bravo AF: 0.817

Asia WGS AF: 0.742 AC: 2578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.4
DANN	Benign	0.93

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: rs7959129; hg19: chr12-51169108;