rs7922341

chr10-14910793-A-Cchr10-14910793-A-Gchr10-14910793-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DCLRE1C	NM_001033855.3	c.1157-1463T>G		intron_variant		ENST00000378278.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.1157-1463T>G		intron_variant		1	NM_001033855.3	P2

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

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.255

Alfa AF: 0.182 Hom.: 2062

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

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

Other links and lift over

dbSNP: rs7922341; hg19: chr10-14952792;