3-48455358-A-G

Variant names:

• chr3-48455358-A-G
• rs6776700
• NM_130384.3:c.671+940A>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.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
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130384.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	NM_130384.3	MANE Select	c.671+940A>G		intron	N/A	NP_569055.1
	ATRIP	NM_032166.4		c.671+940A>G		intron	N/A	NP_115542.2
	ATRIP	NM_001271023.2		c.392+940A>G		intron	N/A	NP_001257952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.671+940A>G		intron	N/A	ENSP00000323099.3
	ATRIP	ENST00000346691.9	TSL:1	c.671+940A>G		intron	N/A	ENSP00000302338.5
	ATRIP	ENST00000412052.4	TSL:1	c.392+940A>G		intron	N/A	ENSP00000400930.1

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

African (AFR) AF: 0.725 AC: 30074 AN: 41480

American (AMR) AF: 0.686 AC: 10480 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3468

East Asian (EAS) AF: 0.699 AC: 3609 AN: 5166

South Asian (SAS) AF: 0.678 AC: 3270 AN: 4826

European-Finnish (FIN) AF: 0.605 AC: 6407 AN: 10582

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36973 AN: 67954

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.577 Hom.: 17552

Bravo AF: 0.633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
PhyloP100		0.076

Splicing

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

Other links and lift over

dbSNP: rs6776700; hg19: chr3-48496758;