rs371036312

Variant names:

• chr3-48466285-ACTGCCTGC-A
• rs371036312
• ENST00000625293:c.-38_-31delCTGCCTGC

Your query was ambiguous. Multiple possible variants found:

• chr3-48466285-ACTGCCTGC-A
• chr3-48466285-ACTGCCTGC-ACTGC
• chr3-48466285-ACTGCCTGC-ACTGCCTGCCTGC
• chr3-48466285-ACTGCCTGC-ACTGCCTGCCTGCCTGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_033629.6(TREX1):​c.-38_-31delCTGCCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 668,026 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (2 hom.)
• Consequence: TREX1 NM_033629.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00188 (286/152250) while in subpopulation AMR AF= 0.00373 (57/15298). AF 95% confidence interval is 0.00295. There are 1 homozygotes in gnomad4. There are 154 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX1	NM_033629.6	c.-38_-31delCTGCCTGC		5_prime_UTR_variant	Exon 1 of 2	ENST00000625293.3	NP_338599.1
ATRIP	NM_130384.3	c.*744_*751delCTGCCTGC		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	c.-38_-31delCTGCCTGC		5_prime_UTR_variant	Exon 1 of 2		NM_033629.6	ENSP00000486676.2
ATRIP	ENST00000320211.10	c.*744_*751delCTGCCTGC		3_prime_UTR_variant	Exon 13 of 13	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152132 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00227 AC: 1173 AN: 515776 Hom.: 2 AF XY: 0.00234 AC XY: 637 AN XY: 271818

Gnomad4 AFR exome AF: 0.000337

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00320

Gnomad4 FIN exome AF: 0.00348

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.00312

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152250 Hom.: 1 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74452

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.0000542 Hom.: 0

Bravo AF: 0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs371036312; hg19: chr3-48507684;