rs1877474

Variant names:

• chr1-212584549-T-C
• rs1877474
• ENST00000366987.6:c.-5+19066T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATF3	NM_001030287.4	c.-5+19066T>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.-5+19066T>C		intron_variant	Intron 1 of 3	1		ENSP00000355954.2
ATF3	ENST00000366981.8	c.-5+19066T>C		intron_variant	Intron 1 of 3	1		ENSP00000355948.4

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

African (AFR) AF: 0.544 AC: 22532 AN: 41410

American (AMR) AF: 0.441 AC: 6742 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1934 AN: 5140

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4814

European-Finnish (FIN) AF: 0.365 AC: 3859 AN: 10564

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25707 AN: 67956

Other (OTH) AF: 0.417 AC: 881 AN: 2114

Alfa AF: 0.389 Hom.: 19261

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
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1877474; hg19: chr1-212757891;