3-48455358-A-G

Position:

• chr3-48455358-A-G

Variant summary

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

The NM_130384.3(ATRIP):​c.671+940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,068 control chromosomes in the GnomAD database, including 29,854 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 0.62 (29854 hom., cov: 32)
• Consequence: ATRIP NM_130384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRIP	NM_130384.3	c.671+940A>G		intron_variant		ENST00000320211.10
ATRIP-TREX1	NR_153405.1	n.738+940A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10	c.671+940A>G		intron_variant		1	NM_130384.3	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94527 AN: 151950 Hom.: 29801 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.622 AC: 94641 AN: 152068 Hom.: 29854 Cov.: 32 AF XY: 0.627 AC XY: 46643 AN XY: 74346

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.618

Alfa AF: 0.574 Hom.: 11855

Bravo AF: 0.633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6776700; hg19: chr3-48496758;