Variant rs35927251 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001033855.3(DCLRE1C):c.780+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,202 control chromosomes in the GnomAD database, including 24,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2351 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22047 hom. )

Consequence

DCLRE1C
NM_001033855.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.75

Variant links:

Genes affected

DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DCLRE1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 10-14932844-G-A is Benign according to our data. Variant chr10-14932844-G-A is described in ClinVar as [Benign]. Clinvar id is 257181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLRE1C	NM_001033855.3 linkuse as main transcript	c.780+10C>T		intron_variant		ENST00000378278.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLRE1C	ENST00000378278.7 linkuse as main transcript	c.780+10C>T		intron_variant		1	NM_001033855.3	P2	Q96SD1-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26414

AN:

151960

Hom.:

2345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0968

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.166

AC:

41658

AN:

251442

Hom.:

3622

AF XY:

0.161

AC XY:

21901

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.171

AC:

250280

AN:

1460122

Hom.:

22047

Cov.:

AF XY:

0.169

AC XY:

122867

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0978

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.174

AC:

26450

AN:

152080

Hom.:

2351

Cov.:

AF XY:

0.175

AC XY:

12995

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0962

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.153

Hom.:

949

Bravo

AF:

0.180

Asia WGS

AF:

0.109

AC:

379

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Histiocytic medullary reticulosis

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.55

Position offset: 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