rs7906952

Variant names:

• chr10-14943303-T-C
• rs7906952
• NM_001033855.3:c.246+1802A>G

Variant summary

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

The NM_001033855.3(DCLRE1C):​c.246+1802A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 151,882 control chromosomes in the GnomAD database, including 50,851 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 0.81 (50851 hom., cov: 30)
• Consequence: DCLRE1C NM_001033855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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, Orphanet, Ambry Genetics
• severe combined immunodeficiency due to DCLRE1C deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1C	NM_001033855.3	MANE Select	c.246+1802A>G		intron	N/A	NP_001029027.1	Q96SD1-1
	DCLRE1C	NM_001350965.2		c.246+1802A>G		intron	N/A	NP_001337894.1	A0A8V8TKN9
	DCLRE1C	NM_001289076.2		c.-43-3434A>G		intron	N/A	NP_001276005.1	Q96SD1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1C	ENST00000378278.7	TSL:1 MANE Select	c.246+1802A>G		intron	N/A	ENSP00000367527.2	Q96SD1-1
	DCLRE1C	ENST00000378289.8	TSL:1	c.246+1802A>G		intron	N/A	ENSP00000367538.4	Q96SD1-4
	DCLRE1C	ENST00000357717.6	TSL:1	n.162-3434A>G		intron	N/A	ENSP00000350349.3	A0A9S7JGJ5

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123392 AN: 151764 Hom.: 50789 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.813 AC: 123514 AN: 151882 Hom.: 50851 Cov.: 30 AF XY: 0.815 AC XY: 60494 AN XY: 74218

African (AFR) AF: 0.943 AC: 38999 AN: 41342

American (AMR) AF: 0.829 AC: 12647 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2573 AN: 3468

East Asian (EAS) AF: 0.906 AC: 4669 AN: 5156

South Asian (SAS) AF: 0.803 AC: 3867 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7622 AN: 10572

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.744 AC: 50558 AN: 67958

Other (OTH) AF: 0.788 AC: 1665 AN: 2114

Alfa AF: 0.782 Hom.: 67772

Bravo AF: 0.828

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-1.9
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: rs7906952; hg19: chr10-14985302;