rs922075

Variant names:

• chr3-48447994-A-G
• rs922075
• NM_130384.3:c.247+902A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-48447994-A-G
• chr3-48447994-A-T

Variant summary

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

The NM_130384.3(ATRIP):​c.247+902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,942 control chromosomes in the GnomAD database, including 19,715 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 0.49 (19715 hom., cov: 31)
• Consequence: ATRIP NM_130384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 12 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=-0.81).
• 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.247+902A>G		intron_variant	Intron 1 of 12	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.247+902A>G		intron_variant	Intron 1 of 12	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74793 AN: 151824 Hom.: 19701 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.493 AC: 74840 AN: 151942 Hom.: 19715 Cov.: 31 AF XY: 0.502 AC XY: 37252 AN XY: 74278

African (AFR) AF: 0.288 AC: 11948 AN: 41434

American (AMR) AF: 0.625 AC: 9543 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3613 AN: 5174

South Asian (SAS) AF: 0.674 AC: 3242 AN: 4812

European-Finnish (FIN) AF: 0.606 AC: 6383 AN: 10526

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36646 AN: 67948

Other (OTH) AF: 0.518 AC: 1091 AN: 2108

Alfa AF: 0.509 Hom.: 29460

Bravo AF: 0.483

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.69
PhyloP100		2.6
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: rs922075; hg19: chr3-48489398;