3-48464565-A-C

Variant names:

• chr3-48464565-A-C
• rs2242150
• NM_130384.3:c.1975-17A>C

Variant summary

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

The NM_130384.3(ATRIP):​c.1975-17A>C variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATRIP-TREX1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.1975-17A>C		intron_variant	Intron 10 of 12	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.1975-17A>C		intron_variant	Intron 10 of 12	1	NM_130384.3	ENSP00000323099.3

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

African (AFR) AF: 0.543 AC: 18171 AN: 33454

American (AMR) AF: 0.749 AC: 33496 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 13521 AN: 26132

East Asian (EAS) AF: 0.668 AC: 26527 AN: 39690

South Asian (SAS) AF: 0.669 AC: 57712 AN: 86240

European-Finnish (FIN) AF: 0.605 AC: 32299 AN: 53398

Middle Eastern (MID) AF: 0.616 AC: 3549 AN: 5764

European-Non Finnish (NFE) AF: 0.539 AC: 599018 AN: 1110980

Other (OTH) AF: 0.564 AC: 34018 AN: 60368

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

African (AFR) AF: 0.537 AC: 22256 AN: 41476

American (AMR) AF: 0.662 AC: 10112 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3466

East Asian (EAS) AF: 0.698 AC: 3607 AN: 5166

South Asian (SAS) AF: 0.677 AC: 3257 AN: 4814

European-Finnish (FIN) AF: 0.606 AC: 6401 AN: 10570

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36840 AN: 67938

Other (OTH) AF: 0.576 AC: 1213 AN: 2106

Alfa AF: 0.553 Hom.: 58377

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
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs2242150; hg19: chr3-48505964;