rs6691852

Variant names:

• chr1-212597080-T-C
• rs6691852
• ENST00000366987.6:c.-4-17938T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001030287.4(ATF3):​c.-4-17938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,232 control chromosomes in the GnomAD database, including 58,411 homozygotes. 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 0.87 (58411 hom., cov: 31)
• Consequence: ATF3 NM_001030287.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

Genes affected

ATF3 (HGNC:785): (activating transcription factor 3) This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes. [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF3	NM_001030287.4	c.-4-17938T>C		intron_variant	Intron 1 of 3		NP_001025458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF3	ENST00000366987.6	c.-4-17938T>C		intron_variant	Intron 1 of 3	1		ENSP00000355954.2
ATF3	ENST00000366981.8	c.-4-17938T>C		intron_variant	Intron 1 of 3	1		ENSP00000355948.4

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132697 AN: 152114 Hom.: 58383 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.872 AC: 132778 AN: 152232 Hom.: 58411 Cov.: 31 AF XY: 0.870 AC XY: 64735 AN XY: 74434

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.887

Alfa AF: 0.880 Hom.: 26796

Bravo AF: 0.850

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.71

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: rs6691852; hg19: chr1-212770422;