rs12572872

Variant names:

• chr10-14912025-G-A
• rs12572872
• NM_001033855.3:c.1157-2695C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033855.3(DCLRE1C):​c.1157-2695C>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
• Publications: 12 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=-0.91).
• 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 rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.1157-2695C>T		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.1157-2695C>T		intron_variant	Intron 13 of 13	1	NM_001033855.3	ENSP00000367527.2

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

African (AFR) AF: 0.643 AC: 26655 AN: 41482

American (AMR) AF: 0.317 AC: 4843 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2082 AN: 5182

South Asian (SAS) AF: 0.474 AC: 2279 AN: 4812

European-Finnish (FIN) AF: 0.190 AC: 2012 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17424 AN: 67980

Other (OTH) AF: 0.351 AC: 741 AN: 2110

Alfa AF: 0.298 Hom.: 13026

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
PhyloP100		-0.10
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: rs12572872; hg19: chr10-14954024;