1-212574805-T-C

Position:

• chr1-212574805-T-C

Variant summary

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

The ENST00000366987.6(ATF3):​c.-5+9322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,936 control chromosomes in the GnomAD database, including 19,526 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 0.51 (19526 hom., cov: 32)
• Consequence: ATF3 ENST00000366987.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF3	NM_001030287.4	c.-5+9322T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF3	ENST00000366981.8	c.-5+9322T>C		intron_variant		1
ATF3	ENST00000366987.6	c.-5+9322T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77036 AN: 151818 Hom.: 19505 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.507 AC: 77094 AN: 151936 Hom.: 19526 Cov.: 32 AF XY: 0.506 AC XY: 37551 AN XY: 74236

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.519

Alfa AF: 0.506 Hom.: 37174

Bravo AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.37

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: rs3125289; hg19: chr1-212748147;