10-14949431-A-C

Variant names:

• chr10-14949431-A-C
• rs7906967
• NM_001033855.3:c.110-344T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033855.3(DCLRE1C):​c.110-344T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,276 control chromosomes in the GnomAD database, including 1,089 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1089 hom., cov: 32)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.110-344T>G		intron_variant	Intron 1 of 13	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.110-344T>G		intron_variant	Intron 1 of 13	1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15407 AN: 152158 Hom.: 1084 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00538

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15446 AN: 152276 Hom.: 1089 Cov.: 32 AF XY: 0.103 AC XY: 7696 AN XY: 74460

African (AFR) AF: 0.187 AC: 7790 AN: 41552

American (AMR) AF: 0.0863 AC: 1320 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3466

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5188

South Asian (SAS) AF: 0.0553 AC: 267 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1160 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4485 AN: 68026

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0871 Hom.: 143

Bravo AF: 0.105

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.36
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7906967; hg19: chr10-14991430;