chr3-48463833-C-T

Variant names:

• chr3-48463833-C-T
• rs34426134
• NM_130384.3:c.1834C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000320211.10(ATRIP):​c.1834C>T​(p.Leu612Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,614,142 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (32 hom.)
• Consequence: ATRIP ENST00000320211.10 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.221
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-48463833-C-T is Benign according to our data. Variant chr3-48463833-C-T is described in ClinVar as Benign. ClinVar VariationId is 783377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.221 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1996/152256) while in subpopulation AFR AF = 0.0458 (1901/41532). AF 95% confidence interval is 0.0441. There are 46 homozygotes in GnomAd4. There are 962 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000320211.10. 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.1834C>T	p.Leu612Leu	synonymous	Exon 9 of 13	NP_569055.1
	ATRIP	NM_032166.4		c.1834C>T	p.Leu612Leu	synonymous	Exon 9 of 12	NP_115542.2
	ATRIP	NM_001271023.2		c.1555C>T	p.Leu519Leu	synonymous	Exon 9 of 13	NP_001257952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.1834C>T	p.Leu612Leu	synonymous	Exon 9 of 13	ENSP00000323099.3
	ATRIP	ENST00000346691.9	TSL:1	c.1834C>T	p.Leu612Leu	synonymous	Exon 9 of 12	ENSP00000302338.5
	ATRIP	ENST00000412052.4	TSL:1	c.1555C>T	p.Leu519Leu	synonymous	Exon 9 of 13	ENSP00000400930.1

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1992 AN: 152138 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00329 AC: 828 AN: 251436 AF XY: 0.00241

Gnomad AFR exome AF: 0.0449

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00136 AC: 1986 AN: 1461886 Hom.: 32 Cov.: 31 AF XY: 0.00119 AC XY: 864 AN XY: 727244

African (AFR) AF: 0.0468 AC: 1567 AN: 33480

American (AMR) AF: 0.00224 AC: 100 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1112010

Other (OTH) AF: 0.00285 AC: 172 AN: 60394

GnomAD4 genome AF: 0.0131 AC: 1996 AN: 152256 Hom.: 46 Cov.: 32 AF XY: 0.0129 AC XY: 962 AN XY: 74450

African (AFR) AF: 0.0458 AC: 1901 AN: 41532

American (AMR) AF: 0.00419 AC: 64 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00608 Hom.: 9

Bravo AF: 0.0147

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs34426134; hg19: chr3-48505232;