rs12572872

chr10-14912025-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.1157-2695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,086 control chromosomes in the GnomAD database, including 13,141 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 0.38 (13141 hom., cov: 32)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLRE1C	NM_001033855.3	c.1157-2695C>T		intron_variant		ENST00000378278.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.1157-2695C>T		intron_variant		1	NM_001033855.3	P2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57561 AN: 151968 Hom.: 13088 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.379 AC: 57681 AN: 152086 Hom.: 13141 Cov.: 32 AF XY: 0.380 AC XY: 28273 AN XY: 74360

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.351

Alfa AF: 0.287 Hom.: 9308

Bravo AF: 0.398

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.2
Dann	Benign	0.66

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: rs12572872; hg19: chr10-14954024;