rs6442123

Positions:

• chr3-48458887-A-G
• chr3-48458887-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
ATRIP	NM_130384.3	c.830-472A>G		intron_variant		ENST00000320211.10	NP_569055.1
ATRIP-TREX1	NR_153405.1	n.897-472A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATRIP	ENST00000320211.10	c.830-472A>G		intron_variant		1	NM_130384.3	ENSP00000323099	P1

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

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.577

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6442123; hg19: chr3-48500286;