Genetic Variant DCLRE1A:c.*186G>A (chr10-113834966-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

5 publications found

Variant links:

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]

DCLRE1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1A	NM_014881.5 link	c.*186G>A	3_prime_UTR_variant	Exon 9 of 9	ENST00000361384.7	NP_055696.3	Q6PJP8
DCLRE1A	NM_001271816.2 link	c.*186G>A	3_prime_UTR_variant	Exon 10 of 10		NP_001258745.1	Q6PJP8
DCLRE1A	XM_006718090.2 link	c.*186G>A	3_prime_UTR_variant	Exon 10 of 10		XP_006718153.1	Q6PJP8
DCLRE1A	XM_011540429.2 link	c.*186G>A	3_prime_UTR_variant	Exon 10 of 10		XP_011538731.1	Q6PJP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7 link	c.*186G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_014881.5	ENSP00000355185.2		Q6PJP8
DCLRE1A	ENST00000369305.1 link	c.*186G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000358311.1		Q6PJP8

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2479

AN:

152160

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0192

AC XY:

4259

AN XY:

221876

show subpopulations

African (AFR)

AF:

0.00477

AC:

AN:

10474

American (AMR)

AF:

0.0190

AC:

236

AN:

12412

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

224

AN:

12140

East Asian (EAS)

AF:

0.00

AC:

AN:

25778

South Asian (SAS)

AF:

0.00616

AC:

202

AN:

32810

European-Finnish (FIN)

AF:

0.00752

AC:

196

AN:

26072

Middle Eastern (MID)

AF:

0.0255

AC:

AN:

1802

European-Non Finnish (NFE)

AF:

0.0251

AC:

7021

AN:

280258

Other (OTH)

AF:

0.0189

AC:

451

AN:

23858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

388

777

1165

1554

1942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0163

AC:

2475

AN:

152278

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1122

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00541

AC:

225

AN:

41566

American (AMR)

AF:

0.0233

AC:

356

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00519

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00970

AC:

103

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1601

AN:

68022

Other (OTH)

AF:

0.0246

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

129

258

386

515

644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0235

Hom.:

108

Bravo

AF:

0.0177

Asia WGS

AF:

0.00202

AC:

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

(source)

DANN

Benign

0.36

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over