rs7076862

Variant names:

• chr10-14934415-G-A
• rs7076862
• NM_001033855.3:c.643C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-14934415-G-A
• chr10-14934415-G-C
• chr10-14934415-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001033855.3(DCLRE1C):​c.643C>T​(p.Leu215Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.394 in 1,613,398 control chromosomes in the GnomAD database, including 131,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16737 hom., cov: 30)
  • Exomes 𝑓: 0.39 (114476 hom.)
• Consequence: DCLRE1C NM_001033855.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11 O:1
• Conservation: PhyloP100: 3.65
• Publications: 20 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 10-14934415-G-A is Benign according to our data. Variant chr10-14934415-G-A is described in ClinVar as Benign. ClinVar VariationId is 36000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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.643C>T	p.Leu215Leu	synonymous	Exon 8 of 14	NP_001029027.1
	DCLRE1C	NM_001350965.2		c.643C>T	p.Leu215Leu	synonymous	Exon 8 of 15	NP_001337894.1
	DCLRE1C	NM_001289076.2		c.298C>T	p.Leu100Leu	synonymous	Exon 6 of 12	NP_001276005.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1C	ENST00000378278.7	TSL:1 MANE Select	c.643C>T	p.Leu215Leu	synonymous	Exon 8 of 14	ENSP00000367527.2
	DCLRE1C	ENST00000378289.8	TSL:1	c.643C>T	p.Leu215Leu	synonymous	Exon 8 of 14	ENSP00000367538.4
	DCLRE1C	ENST00000357717.6	TSL:1	n.*301C>T		non_coding_transcript_exon	Exon 6 of 12	ENSP00000350349.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68424 AN: 151738 Hom.: 16692 Cov.: 30

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.416 AC: 104558 AN: 251182 AF XY: 0.416

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.409

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.388 AC: 567459 AN: 1461544 Hom.: 114476 Cov.: 61 AF XY: 0.393 AC XY: 285397 AN XY: 727062

African (AFR) AF: 0.663 AC: 22188 AN: 33448

American (AMR) AF: 0.472 AC: 21097 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 11382 AN: 26130

East Asian (EAS) AF: 0.471 AC: 18696 AN: 39698

South Asian (SAS) AF: 0.550 AC: 47403 AN: 86188

European-Finnish (FIN) AF: 0.262 AC: 14010 AN: 53410

Middle Eastern (MID) AF: 0.462 AC: 2664 AN: 5768

European-Non Finnish (NFE) AF: 0.365 AC: 405588 AN: 1111848

Other (OTH) AF: 0.405 AC: 24431 AN: 60386

GnomAD4 genome AF: 0.451 AC: 68536 AN: 151854 Hom.: 16737 Cov.: 30 AF XY: 0.450 AC XY: 33393 AN XY: 74214

African (AFR) AF: 0.647 AC: 26770 AN: 41376

American (AMR) AF: 0.442 AC: 6740 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1495 AN: 3462

East Asian (EAS) AF: 0.419 AC: 2167 AN: 5178

South Asian (SAS) AF: 0.543 AC: 2612 AN: 4806

European-Finnish (FIN) AF: 0.265 AC: 2787 AN: 10534

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24479 AN: 67934

Other (OTH) AF: 0.444 AC: 932 AN: 2100

Alfa AF: 0.384 Hom.: 4954

Bravo AF: 0.472

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Histiocytic medullary reticulosis (3)
-	-	3	not specified (3)
-	-	2	not provided (3)
-	-	2	Severe combined immunodeficiency due to DCLRE1C deficiency (2)
-	-	1	Severe combined immunodeficiency disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		3.7
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: rs7076862; hg19: chr10-14976414; COSMIC: COSV63182212; COSMIC: COSV63182212;