rs7626978

Variant names:

• chr3-48464432-T-G
• rs7626978
• NM_130384.3:c.1975-150T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130384.3(ATRIP):​c.1975-150T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 938,796 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (291 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (191 hom.)
• Consequence: ATRIP NM_130384.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.730
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-48464432-T-G is Benign according to our data. Variant chr3-48464432-T-G is described in ClinVar as [Benign]. Clinvar id is 1238999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.1975-150T>G		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.1975-150T>G		intron_variant	Intron 10 of 12	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5298 AN: 152160 Hom.: 283 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.00542 AC: 4261 AN: 786518 Hom.: 191 AF XY: 0.00484 AC XY: 1966 AN XY: 406596

African (AFR) AF: 0.127 AC: 2513 AN: 19832

American (AMR) AF: 0.00943 AC: 330 AN: 34990

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 310 AN: 17966

East Asian (EAS) AF: 0.00 AC: 0 AN: 35824

South Asian (SAS) AF: 0.000494 AC: 31 AN: 62732

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 39086

Middle Eastern (MID) AF: 0.0164 AC: 69 AN: 4220

European-Non Finnish (NFE) AF: 0.00104 AC: 556 AN: 534296

Other (OTH) AF: 0.0120 AC: 451 AN: 37572

GnomAD4 genome AF: 0.0351 AC: 5340 AN: 152278 Hom.: 291 Cov.: 33 AF XY: 0.0348 AC XY: 2593 AN XY: 74472

African (AFR) AF: 0.117 AC: 4873 AN: 41532

American (AMR) AF: 0.0148 AC: 226 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00159 AC: 108 AN: 68014

Other (OTH) AF: 0.0269 AC: 57 AN: 2116

Alfa AF: 0.0247 Hom.: 312

Bravo AF: 0.0401

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7626978; hg19: chr3-48505831;