NM_001033855.3:c.780+10C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:10

Conservation

PhyloP100: -1.75

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

Omenn syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet
severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

DCLRE1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious 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 VariationId 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 rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3 link	c.780+10C>T		intron_variant	Intron 9 of 13	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7 link	c.780+10C>T		intron_variant	Intron 9 of 13	1	NM_001033855.3	ENSP00000367527.2

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

GnomAD2 exomes

AF:

0.166

AC:

41658

AN:

251442

AF XY:

0.161

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 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

African (AFR)

AF:

0.193

AC:

6469

AN:

33462

American (AMR)

AF:

0.234

AC:

10476

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3172

AN:

26128

East Asian (EAS)

AF:

0.0978

AC:

3884

AN:

39698

South Asian (SAS)

AF:

0.129

AC:

11101

AN:

86222

European-Finnish (FIN)

AF:

0.154

AC:

8233

AN:

53416

Middle Eastern (MID)

AF:

0.196

AC:

1131

AN:

5764

European-Non Finnish (NFE)

AF:

0.176

AC:

195561

AN:

1110384

Other (OTH)

AF:

0.170

AC:

10253

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

10520

21040

31560

42080

52600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6968

13936

20904

27872

34840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26450

AN:

152080

Hom.:

2351

Cov.:

AF XY:

0.175

AC XY:

12995

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.185

AC:

7689

AN:

41452

American (AMR)

AF:

0.210

AC:

3200

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3472

East Asian (EAS)

AF:

0.0962

AC:

499

AN:

5186

South Asian (SAS)

AF:

0.124

AC:

598

AN:

4830

European-Finnish (FIN)

AF:

0.166

AC:

1754

AN:

10576

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11745

AN:

67990

Other (OTH)

AF:

0.163

AC:

343

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1094

2188

3282

4376

5470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

1104

Bravo

AF:

0.180

Asia WGS

AF:

0.109

AC:

379

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 24, 2024

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 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Histiocytic medullary reticulosis

Benign:3

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

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

Benign

-0.94

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over