rs7900814

Variant names:

• chr10-14909662-G-A
• rs7900814
• NM_001033855.3:c.1157-332C>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.1157-332C>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
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033855.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1C	NM_001033855.3	MANE Select	c.1157-332C>T		intron	N/A	NP_001029027.1
	DCLRE1C	NM_001350965.2		c.1157-332C>T		intron	N/A	NP_001337894.1
	DCLRE1C	NM_001289076.2		c.812-332C>T		intron	N/A	NP_001276005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1C	ENST00000378278.7	TSL:1 MANE Select	c.1157-332C>T		intron	N/A	ENSP00000367527.2
	DCLRE1C	ENST00000378289.8	TSL:1	c.1156+10076C>T		intron	N/A	ENSP00000367538.4
	DCLRE1C	ENST00000357717.6	TSL:1	n.*815-332C>T		intron	N/A	ENSP00000350349.3

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

African (AFR) AF: 0.741 AC: 30692 AN: 41392

American (AMR) AF: 0.421 AC: 6432 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1435 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3048 AN: 5158

South Asian (SAS) AF: 0.567 AC: 2726 AN: 4812

European-Finnish (FIN) AF: 0.239 AC: 2490 AN: 10436

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21076 AN: 67946

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.429 Hom.: 14665

Bravo AF: 0.480

Asia WGS AF: 0.569 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.47
PhyloP100		-0.90
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: rs7900814; hg19: chr10-14951661;