10-113834966-C-T

Position:

• chr10-113834966-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014881.5(DCLRE1A):​c.*186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 577,882 control chromosomes in the GnomAD database, including 139 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 0.016 (37 hom., cov: 32)
  • Exomes 𝑓: 0.020 (102 hom.)
• Consequence: DCLRE1A NM_014881.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

DCLRE1A (HGNC:17660): (DNA cross-link repair 1A) This gene encodes a conserved protein that is involved in the repair of DNA interstrand cross-links. DNA cross-links suppress transcription, replication, and DNA segregation. The encoded protein is a regulator of the mitotic cell cycle checkpoint. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2475/152278) while in subpopulation NFE AF= 0.0235 (1601/68022). AF 95% confidence interval is 0.0226. There are 37 homozygotes in gnomad4. There are 1122 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1A	NM_014881.5	c.*186G>A		3_prime_UTR_variant	9/9	ENST00000361384.7	NP_055696.3
DCLRE1A	NM_001271816.2	c.*186G>A		3_prime_UTR_variant	10/10		NP_001258745.1
DCLRE1A	XM_006718090.2	c.*186G>A		3_prime_UTR_variant	10/10		XP_006718153.1
DCLRE1A	XM_011540429.2	c.*186G>A		3_prime_UTR_variant	10/10		XP_011538731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7	c.*186G>A		3_prime_UTR_variant	9/9	1	NM_014881.5	ENSP00000355185	P1
DCLRE1A	ENST00000369305.1	c.*186G>A		3_prime_UTR_variant	10/10	5		ENSP00000358311	P1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2479 AN: 152160 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00543

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0198 AC: 8426 AN: 425604 Hom.: 102 Cov.: 6 AF XY: 0.0192 AC XY: 4259 AN XY: 221876

Gnomad4 AFR exome AF: 0.00477

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00616

Gnomad4 FIN exome AF: 0.00752

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0163 AC: 2475 AN: 152278 Hom.: 37 Cov.: 32 AF XY: 0.0151 AC XY: 1122 AN XY: 74460

Gnomad4 AFR AF: 0.00541

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00519

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0243 Hom.: 50

Bravo AF: 0.0177

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs10567; hg19: chr10-115594725;