NM_130384.3:c.830-472A>G

Variant names:

• chr3-48458887-A-G
• rs6442123
• NM_130384.3:c.830-472A>G

Variant summary

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

The NM_130384.3(ATRIP):​c.830-472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,058 control chromosomes in the GnomAD database, including 24,628 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 (24628 hom., cov: 32)
• Consequence: ATRIP NM_130384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.830-472A>G		intron_variant	Intron 5 of 12	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.830-472A>G		intron_variant	Intron 5 of 12	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86308 AN: 151938 Hom.: 24608 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.568 AC: 86372 AN: 152058 Hom.: 24628 Cov.: 32 AF XY: 0.575 AC XY: 42716 AN XY: 74306

African (AFR) AF: 0.541 AC: 22436 AN: 41460

American (AMR) AF: 0.663 AC: 10123 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3613 AN: 5170

South Asian (SAS) AF: 0.676 AC: 3256 AN: 4818

European-Finnish (FIN) AF: 0.606 AC: 6404 AN: 10566

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

European-Non Finnish (NFE) AF: 0.542 AC: 36869 AN: 67982

Other (OTH) AF: 0.577 AC: 1217 AN: 2108

Alfa AF: 0.440 Hom.: 1271

Bravo AF: 0.570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs6442123; hg19: chr3-48500286;