chr12-50764080-G-C

Variant names:

• chr12-50764080-G-C
• rs61926301
• NM_001412963.1:c.-7+339G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001412963.1(ATF1):​c.-7+339G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 143,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000028 (0 hom., cov: 25)
• Consequence: ATF1 NM_001412963.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000279 AC: 4 AN: 143550 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000697

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000279 AC: 4 AN: 143550 Hom.: 0 Cov.: 25 AF XY: 0.0000144 AC XY: 1 AN XY: 69540

Gnomad4 AFR AF: 0.0000511

Gnomad4 AMR AF: 0.0000697

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000317 Hom.: 2113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.69

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;