rs1877474

Positions:

• chr1-212584549-T-C
• chr1-212584549-T-G

Variant summary

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

The ENST00000366987.6(ATF3):​c.-5+19066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,952 control chromosomes in the GnomAD database, including 14,126 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 0.42 (14126 hom., cov: 31)
• Consequence: ATF3 ENST00000366987.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF3	NM_001030287.4	c.-5+19066T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF3	ENST00000366981.8	c.-5+19066T>C		intron_variant		1
ATF3	ENST00000366987.6	c.-5+19066T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64202 AN: 151832 Hom.: 14090 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.423 AC: 64290 AN: 151952 Hom.: 14126 Cov.: 31 AF XY: 0.416 AC XY: 30867 AN XY: 74256

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.417

Alfa AF: 0.381 Hom.: 14619

Bravo AF: 0.445

Asia WGS AF: 0.284 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.54

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: rs1877474; hg19: chr1-212757891;