1-212574805-T-C

Variant names:

• chr1-212574805-T-C
• rs3125289
• ENST00000366987.6:c.-5+9322T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001030287.4(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 NM_001030287.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030287.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF3	NM_001030287.4		c.-5+9322T>C		intron	N/A	NP_001025458.1	P18847-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF3	ENST00000366987.6	TSL:1	c.-5+9322T>C		intron	N/A	ENSP00000355954.2	P18847-1
	ATF3	ENST00000366981.8	TSL:1	c.-5+9322T>C		intron	N/A	ENSP00000355948.4	Q5VTZ4

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

African (AFR) AF: 0.483 AC: 20053 AN: 41476

American (AMR) AF: 0.549 AC: 8397 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1687 AN: 3464

East Asian (EAS) AF: 0.547 AC: 2826 AN: 5164

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5436 AN: 10528

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35003 AN: 67882

Other (OTH) AF: 0.519 AC: 1094 AN: 2106

Alfa AF: 0.508 Hom.: 50107

Bravo AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.37
PhyloP100		-1.4
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: rs3125289; hg19: chr1-212748147;