NM_001033855.3:c.1157-1463T>G

Variant names:

• chr10-14910793-A-C
• rs7922341
• NM_001033855.3:c.1157-1463T>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.1157-1463T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,960 control chromosomes in the GnomAD database, including 7,283 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 0.28 (7283 hom., cov: 32)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.1157-1463T>G		intron_variant	Intron 13 of 13	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.1157-1463T>G		intron_variant	Intron 13 of 13	1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41834 AN: 151842 Hom.: 7258 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.276 AC: 41916 AN: 151960 Hom.: 7283 Cov.: 32 AF XY: 0.280 AC XY: 20838 AN XY: 74298

African (AFR) AF: 0.461 AC: 19064 AN: 41388

American (AMR) AF: 0.313 AC: 4770 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 993 AN: 3460

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5162

South Asian (SAS) AF: 0.472 AC: 2270 AN: 4814

European-Finnish (FIN) AF: 0.0916 AC: 969 AN: 10578

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10750 AN: 67986

Other (OTH) AF: 0.255 AC: 539 AN: 2110

Alfa AF: 0.180 Hom.: 2782

Bravo AF: 0.298

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.71
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7922341; hg19: chr10-14952792;