rs2242150

Positions:

• chr3-48464565-A-C

Variant summary

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

The NM_130384.3(ATRIP):​c.1975-17A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,612,758 control chromosomes in the GnomAD database, including 256,364 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 0.57 (24519 hom., cov: 32)
  • Exomes 𝑓: 0.56 (231845 hom.)
• Consequence: ATRIP NM_130384.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

Genes affected

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP-TREX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRIP	NM_130384.3	c.1975-17A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000320211.10
ATRIP-TREX1	NR_153405.1	n.2127-17A>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10	c.1975-17A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_130384.3	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86072 AN: 151894 Hom.: 24499 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.560 AC: 818311 AN: 1460744 Hom.: 231845 Cov.: 41 AF XY: 0.562 AC XY: 408417 AN XY: 726702

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.749

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.605

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.567 AC: 86136 AN: 152014 Hom.: 24519 Cov.: 32 AF XY: 0.573 AC XY: 42601 AN XY: 74298

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.576

Alfa AF: 0.552 Hom.: 32035

Bravo AF: 0.568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2242150; hg19: chr3-48505964;