rs7076862

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001033855.3(DCLRE1C):c.643C>T(p.Leu215Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.394 in 1,613,398 control chromosomes in the GnomAD database, including 131,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16737 hom., cov: 30)

Exomes 𝑓: 0.39 ( 114476 hom. )

Consequence

DCLRE1C
NM_001033855.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 3.65

Publications

20 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 10-14934415-G-A is Benign according to our data. Variant chr10-14934415-G-A is described in ClinVar as Benign. ClinVar VariationId is 36000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 8 of 14	ENST00000378278.7	NP_001029027.1	Q96SD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 8 of 14	1	NM_001033855.3	ENSP00000367527.2		Q96SD1-1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68424

AN:

151738

Hom.:

16692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.646

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.416

AC:

104558

AN:

251182

AF XY:

0.416

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.388

AC:

567459

AN:

1461544

Hom.:

114476

Cov.:

AF XY:

0.393

AC XY:

285397

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.663

AC:

22188

AN:

33448

American (AMR)

AF:

0.472

AC:

21097

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11382

AN:

26130

East Asian (EAS)

AF:

0.471

AC:

18696

AN:

39698

South Asian (SAS)

AF:

0.550

AC:

47403

AN:

86188

European-Finnish (FIN)

AF:

0.262

AC:

14010

AN:

53410

Middle Eastern (MID)

AF:

0.462

AC:

2664

AN:

5768

European-Non Finnish (NFE)

AF:

0.365

AC:

405588

AN:

1111848

Other (OTH)

AF:

0.405

AC:

24431

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

20392

40783

61175

81566

101958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13234

26468

39702

52936

66170

<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:

0.451

AC:

68536

AN:

151854

Hom.:

16737

Cov.:

AF XY:

0.450

AC XY:

33393

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.647

AC:

26770

AN:

41376

American (AMR)

AF:

0.442

AC:

6740

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1495

AN:

3462

East Asian (EAS)

AF:

0.419

AC:

2167

AN:

5178

South Asian (SAS)

AF:

0.543

AC:

2612

AN:

4806

European-Finnish (FIN)

AF:

0.265

AC:

2787

AN:

10534

Middle Eastern (MID)

AF:

0.507

AC:

148

AN:

292

European-Non Finnish (NFE)

AF:

0.360

AC:

24479

AN:

67934

Other (OTH)

AF:

0.444

AC:

932

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1793

3585

5378

7170

8963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.384

Hom.:

4954

Bravo

AF:

0.472

Asia WGS

AF:

0.454

AC:

1579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

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 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. 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

Jan 12, 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. -

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

- -

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

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

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe combined immunodeficiency disease

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing;curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.6

(source)

DANN

Benign

0.78

PhyloP100

3.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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