rs11593133

Variant names:

• chr10-14953150-G-A
• rs11593133
• NM_001033855.3:c.109+752C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-14953150-G-A
• chr10-14953150-G-C

Variant summary

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

The NM_001033855.3(DCLRE1C):​c.109+752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,152 control chromosomes in the GnomAD database, including 6,472 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 0.29 (6472 hom., cov: 33)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1C	NM_001033855.3	c.109+752C>T		intron_variant	Intron 1 of 13	ENST00000378278.7	NP_001029027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1C	ENST00000378278.7	c.109+752C>T		intron_variant	Intron 1 of 13	1	NM_001033855.3	ENSP00000367527.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43534 AN: 152034 Hom.: 6474 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.286 AC: 43539 AN: 152152 Hom.: 6472 Cov.: 33 AF XY: 0.280 AC XY: 20841 AN XY: 74380

African (AFR) AF: 0.202 AC: 8389 AN: 41518

American (AMR) AF: 0.339 AC: 5183 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1032 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5172

South Asian (SAS) AF: 0.288 AC: 1390 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2368 AN: 10586

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22697 AN: 67984

Other (OTH) AF: 0.294 AC: 622 AN: 2114

Alfa AF: 0.318 Hom.: 14870

Bravo AF: 0.293

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.98
DANN	Benign	0.69
PhyloP100		-0.62
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: rs11593133; hg19: chr10-14995149;