Variant chr3-48465783-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_130384.3(ATRIP):c.*229A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 507,804 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 69 hom., cov: 33)

Exomes 𝑓: 0.029 ( 184 hom. )

Consequence

ATRIP
NM_130384.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.192

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:

ATRIP-TREX1 (HGNC:):

ATRIP-TREX1 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 3-48465783-A-G is Benign according to our data. Variant chr3-48465783-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1191674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3838/152258) while in subpopulation NFE AF= 0.0382 (2601/68024). AF 95% confidence interval is 0.037. There are 69 homozygotes in gnomad4. There are 1788 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRIP	NM_130384.3 linkuse as main transcript	c.*229A>G		3_prime_UTR_variant	13/13	ENST00000320211.10
ATRIP-TREX1	NR_153405.1 linkuse as main transcript	n.2757A>G		non_coding_transcript_exon_variant	14/15

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10 linkuse as main transcript	c.*229A>G	3_prime_UTR_variant	13/13	1	NM_130384.3	P1	Q8WXE1-1
ATRIP	ENST00000634384.2 linkuse as main transcript	c.*229A>G	3_prime_UTR_variant, NMD_transcript_variant	10/11	2
ATRIP	ENST00000635464.1 linkuse as main transcript	c.*1006A>G	3_prime_UTR_variant, NMD_transcript_variant	15/16	5
TREX1	ENST00000433541.1 linkuse as main transcript		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3838

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00806

Gnomad AMI

AF:

0.0484

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0282

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0383

Gnomad OTH

AF:

0.0158

GnomAD4 exome

AF:

0.0294

AC:

10460

AN:

355546

Hom.:

184

Cov.:

AF XY:

0.0293

AC XY:

5537

AN XY:

189270

show subpopulations

Gnomad4 AFR exome

AF:

0.00711

Gnomad4 AMR exome

AF:

0.0287

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0275

Gnomad4 NFE exome

AF:

0.0372

Gnomad4 OTH exome

AF:

0.0256

GnomAD4 genome

AF:

0.0252

AC:

3838

AN:

152258

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1788

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00804

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0182

Gnomad4 FIN

AF:

0.0282

Gnomad4 NFE

AF:

0.0382

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0339

Hom.:

Bravo

AF:

0.0245

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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