rs115524993

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001033855.3(DCLRE1C):c.1008C>T(p.Asn336Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,614,012 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

DCLRE1C
NM_001033855.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.804

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-14923034-G-A is Benign according to our data. Variant chr10-14923034-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 468481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.804 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00208 (316/152286) while in subpopulation AFR AF = 0.00717 (298/41556). AF 95% confidence interval is 0.0065. There are 2 homozygotes in GnomAd4. There are 150 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3 link	c.1008C>T	p.Asn336Asn	synonymous_variant	Exon 12 of 14	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7 link	c.1008C>T	p.Asn336Asn	synonymous_variant	Exon 12 of 14	1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

312

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000573

AC:

144

AN:

251250

AF XY:

0.000493

show subpopulations

Gnomad AFR exome

AF:

0.00683

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000321

AC:

469

AN:

1461726

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00828

AC:

277

AN:

33468

American (AMR)

AF:

0.000335

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000371

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000935

AC:

104

AN:

1111880

Other (OTH)

AF:

0.000662

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00208

AC:

316

AN:

152286

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00717

AC:

298

AN:

41556

American (AMR)

AF:

0.000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68042

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00107

Hom.:

Bravo

AF:

0.00250

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 06, 2024

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe combined immunodeficiency due to DCLRE1C deficiency

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.83

CADD

Benign

0.61

(source)

DANN

Benign

0.49

PhyloP100

-0.80

Mutation Taster

=296/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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