rs11797

Variant names:

• chr3-48467186-T-C
• rs11797
• NM_033629.6:c.531T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 2P and 17B. PP3_Moderate BP6_Very_Strong BP7 BA1

The NM_033629.6(TREX1):​c.531T>C​(p.Tyr177Tyr) variant causes a synonymous 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: TREX1 NM_033629.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41
• Publications: 66 publications found

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 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 -15 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 VariationId is 467831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
TREX1	NM_033629.6	c.531T>C	p.Tyr177Tyr	synonymous_variant	Exon 2 of 2	ENST00000625293.3	NP_338599.1
ATRIP	NM_130384.3	c.*1632T>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREX1	ENST00000625293.3	c.531T>C	p.Tyr177Tyr	synonymous_variant	Exon 2 of 2	6	NM_033629.6	ENSP00000486676.2
ATRIP	ENST00000320211.10	c.*1632T>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_130384.3	ENSP00000323099.3

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

African (AFR) AF: 0.737 AC: 24661 AN: 33480

American (AMR) AF: 0.769 AC: 34395 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14454 AN: 26136

East Asian (EAS) AF: 0.672 AC: 26693 AN: 39700

South Asian (SAS) AF: 0.674 AC: 58161 AN: 86258

European-Finnish (FIN) AF: 0.615 AC: 32767 AN: 53240

Middle Eastern (MID) AF: 0.653 AC: 3767 AN: 5768

European-Non Finnish (NFE) AF: 0.553 AC: 615109 AN: 1111990

Other (OTH) AF: 0.591 AC: 35696 AN: 60394

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

African (AFR) AF: 0.727 AC: 30154 AN: 41496

American (AMR) AF: 0.693 AC: 10583 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3627 AN: 5174

South Asian (SAS) AF: 0.684 AC: 3303 AN: 4832

European-Finnish (FIN) AF: 0.615 AC: 6508 AN: 10576

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37858 AN: 67942

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.592 Hom.: 25746

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

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.49
CADD	Benign	9.0
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs11797; hg19: chr3-48508585;