chr3-48467186-T-C

Position:

• chr3-48467186-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PP3_Moderate BP6_Very_Strong BA1

The ENST00000320211.10(ATRIP):​c.*1632T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,613,772 control chromosomes in the GnomAD database, including 278,001 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30605 hom., cov: 33)
  • Exomes 𝑓: 0.58 (247396 hom.)
• Consequence: ATRIP ENST00000320211.10 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41

Genes affected

TREX1 (HGNC:12269): (three prime repair exonuclease 1) This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

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 -14 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.49
• BP6: Variant 3-48467186-T-C is Benign according to our data. Variant chr3-48467186-T-C is described in ClinVar as [Benign]. Clinvar id is 467831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREX1	NM_033629.6	c.531T>C	p.Tyr177=	synonymous_variant	2/2	ENST00000625293.3	NP_338599.1
ATRIP	NM_130384.3	c.*1632T>C		3_prime_UTR_variant	13/13	ENST00000320211.10	NP_569055.1
ATRIP-TREX1	NR_153405.1	n.3840T>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREX1	ENST00000625293.3	c.531T>C	p.Tyr177=	synonymous_variant	2/2		NM_033629.6	ENSP00000486676	P1
ATRIP	ENST00000320211.10	c.*1632T>C		3_prime_UTR_variant	13/13	1	NM_130384.3	ENSP00000323099	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95883 AN: 151970 Hom.: 30557 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.579 AC: 845703 AN: 1461682 Hom.: 247396 Cov.: 105 AF XY: 0.580 AC XY: 421415 AN XY: 727132

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.769

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.553

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.631 AC: 95992 AN: 152090 Hom.: 30605 Cov.: 33 AF XY: 0.636 AC XY: 47291 AN XY: 74356

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.633

Alfa AF: 0.587 Hom.: 18888

Bravo AF: 0.641

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -

Chilblain lupus 1;C0796126:Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.49
CADD	Benign	9.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11797; hg19: chr3-48508585;