rs7900814

Positions:

• chr10-14909662-G-A

Variant summary

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

The NM_001033855.3(DCLRE1C):​c.1157-332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,792 control chromosomes in the GnomAD database, including 18,607 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 0.46 (18607 hom., cov: 32)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.1157-332C>T		intron_variant		ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.1157-332C>T		intron_variant		1	NM_001033855.3	ENSP00000367527	P2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69172 AN: 151676 Hom.: 18539 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.457 AC: 69305 AN: 151792 Hom.: 18607 Cov.: 32 AF XY: 0.458 AC XY: 33958 AN XY: 74152

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.433

Alfa AF: 0.367 Hom.: 4659

Bravo AF: 0.480

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.47

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: rs7900814; hg19: chr10-14951661;