rs7906952

Positions:

• chr10-14943303-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033855.3(DCLRE1C):​c.246+1802A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 151,882 control chromosomes in the GnomAD database, including 50,851 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 0.81 (50851 hom., cov: 30)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.246+1802A>G		intron_variant		ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.246+1802A>G		intron_variant		1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123392 AN: 151764 Hom.: 50789 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.813 AC: 123514 AN: 151882 Hom.: 50851 Cov.: 30 AF XY: 0.815 AC XY: 60494 AN XY: 74218

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.788

Alfa AF: 0.793 Hom.: 7771

Bravo AF: 0.828

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.31

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: rs7906952; hg19: chr10-14985302;