rs10475

Variant names:

• chr1-212620271-T-C
• rs10475
• NM_001674.4:c.*716T>C

Variant summary

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

The NM_001674.4(ATF3):​c.*716T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 153,034 control chromosomes in the GnomAD database, including 43,965 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 0.75 (43683 hom., cov: 32)
  • Exomes 𝑓: 0.79 (282 hom.)
• Consequence: ATF3 NM_001674.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF3	NM_001674.4	c.*716T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000341491.9	NP_001665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF3	ENST00000341491.9	c.*716T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001674.4	ENSP00000344352.4
ATF3	ENST00000366987.6	c.*716T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000355954.2
ATF3	ENST00000492118.2	n.1597T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114606 AN: 152026 Hom.: 43652 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.789 AC: 702 AN: 890 Hom.: 282 Cov.: 0 AF XY: 0.798 AC XY: 404 AN XY: 506

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.722

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.754 AC: 114699 AN: 152144 Hom.: 43683 Cov.: 32 AF XY: 0.750 AC XY: 55810 AN XY: 74402

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.738

Alfa AF: 0.770 Hom.: 80063

Bravo AF: 0.748

Asia WGS AF: 0.628 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10475; hg19: chr1-212793613;