Variant chr3-48466219-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_130384.3(ATRIP):c.*665C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 576,066 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

ATRIP
NM_130384.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.179

Variant links:

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 links:

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]

TREX1 links:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-48466219-C-T is Benign according to our data. Variant chr3-48466219-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 345767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ATRIP	NM_130384.3 linkuse as main transcript	c.*665C>T	3_prime_UTR_variant	13/13	ENST00000320211.10
ATRIP-TREX1	NR_153405.1 linkuse as main transcript	n.3193C>T	non_coding_transcript_exon_variant	14/15
TREX1	NM_033629.6 linkuse as main transcript		upstream_gene_variant		ENST00000625293.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10 linkuse as main transcript	c.*665C>T		3_prime_UTR_variant	13/13	1	NM_130384.3	P1	Q8WXE1-1
TREX1	ENST00000625293.3 linkuse as main transcript			upstream_gene_variant			NM_033629.6	P1	Q9NSU2-3

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00149

AC:

632

AN:

423798

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

324

AN XY:

223242

show subpopulations

Gnomad4 AFR exome

AF:

0.000165

Gnomad4 AMR exome

AF:

0.000424

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000350

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.000784

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00112

AC:

170

AN:

152268

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.00119

Asia WGS

AF:

0.00289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Aicardi Goutieres syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over