rs41300676

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000378278.7(DCLRE1C):​c.1893C>T​(p.Pro631=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,614,068 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P631P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0057 ( 29 hom. )

Consequence

DCLRE1C
ENST00000378278.7 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.839
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 10-14908594-G-A is Benign according to our data. Variant chr10-14908594-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-14908594-G-A is described in Lovd as [Likely_benign]. Variant chr10-14908594-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.839 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00439 (668/152202) while in subpopulation NFE AF= 0.00629 (428/68016). AF 95% confidence interval is 0.0058. There are 3 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DCLRE1CNM_001033855.3 linkuse as main transcriptc.1893C>T p.Pro631= synonymous_variant 14/14 ENST00000378278.7 NP_001029027.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DCLRE1CENST00000378278.7 linkuse as main transcriptc.1893C>T p.Pro631= synonymous_variant 14/141 NM_001033855.3 ENSP00000367527 P2Q96SD1-1

Frequencies

GnomAD3 genomes
AF:
0.00437
AC:
665
AN:
152084
Hom.:
3
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00570
Gnomad ASJ
AF:
0.00606
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00125
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00628
Gnomad OTH
AF:
0.0101
GnomAD3 exomes
AF:
0.00375
AC:
942
AN:
251202
Hom.:
4
AF XY:
0.00355
AC XY:
482
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00283
Gnomad AMR exome
AF:
0.00332
Gnomad ASJ exome
AF:
0.00566
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00183
Gnomad FIN exome
AF:
0.000416
Gnomad NFE exome
AF:
0.00555
Gnomad OTH exome
AF:
0.00441
GnomAD4 exome
AF:
0.00568
AC:
8299
AN:
1461866
Hom.:
29
Cov.:
32
AF XY:
0.00550
AC XY:
4002
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00305
Gnomad4 AMR exome
AF:
0.00340
Gnomad4 ASJ exome
AF:
0.00559
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00176
Gnomad4 FIN exome
AF:
0.000449
Gnomad4 NFE exome
AF:
0.00665
Gnomad4 OTH exome
AF:
0.00520
GnomAD4 genome
AF:
0.00439
AC:
668
AN:
152202
Hom.:
3
Cov.:
31
AF XY:
0.00417
AC XY:
310
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00248
Gnomad4 AMR
AF:
0.00569
Gnomad4 ASJ
AF:
0.00606
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00125
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00629
Gnomad4 OTH
AF:
0.00995
Alfa
AF:
0.00508
Hom.:
2
Bravo
AF:
0.00472
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00463
EpiControl
AF:
0.00581

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMay 05, 2020- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024DCLRE1C: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:3
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 24, 2014- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 05, 2013This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Histiocytic medullary reticulosis Benign:2
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Severe combined immunodeficiency due to DCLRE1C deficiency;C2700553:Histiocytic medullary reticulosis Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMar 17, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
5.0
DANN
Benign
0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41300676; hg19: chr10-14950593; API