10-113850156-C-G

Variant names:

• chr10-113850156-C-G
• rs3750898
• NM_014881.5:c.949G>C

Variant summary

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

The NM_014881.5(DCLRE1A):​c.949G>C​(p.Asp317His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,613,794 control chromosomes in the GnomAD database, including 467,821 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (36901 hom., cov: 31)
  • Exomes 𝑓: 0.76 (430920 hom.)
• Consequence: DCLRE1A NM_014881.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 33 publications found

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]

ENSG00000288933 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=9.0333407E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLRE1A	NM_014881.5	c.949G>C	p.Asp317His	missense_variant	Exon 2 of 9	ENST00000361384.7	NP_055696.3
DCLRE1A	NM_001271816.2	c.949G>C	p.Asp317His	missense_variant	Exon 3 of 10		NP_001258745.1
DCLRE1A	XM_006718090.2	c.949G>C	p.Asp317His	missense_variant	Exon 3 of 10		XP_006718153.1
DCLRE1A	XM_011540429.2	c.949G>C	p.Asp317His	missense_variant	Exon 3 of 10		XP_011538731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLRE1A	ENST00000361384.7	c.949G>C	p.Asp317His	missense_variant	Exon 2 of 9	1	NM_014881.5	ENSP00000355185.2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102145 AN: 151874 Hom.: 36898 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.705

GnomAD2 exomes AF: 0.770 AC: 193531 AN: 251384 AF XY: 0.772

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.885

Gnomad ASJ exome AF: 0.801

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.764 AC: 1117364 AN: 1461802 Hom.: 430920 Cov.: 69 AF XY: 0.765 AC XY: 556231 AN XY: 727198

African (AFR) AF: 0.359 AC: 12021 AN: 33480

American (AMR) AF: 0.875 AC: 39115 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 21079 AN: 26134

East Asian (EAS) AF: 0.798 AC: 31669 AN: 39698

South Asian (SAS) AF: 0.732 AC: 63118 AN: 86254

European-Finnish (FIN) AF: 0.806 AC: 42998 AN: 53376

Middle Eastern (MID) AF: 0.799 AC: 4609 AN: 5768

European-Non Finnish (NFE) AF: 0.771 AC: 857419 AN: 1111972

Other (OTH) AF: 0.751 AC: 45336 AN: 60396

GnomAD4 genome AF: 0.672 AC: 102173 AN: 151992 Hom.: 36901 Cov.: 31 AF XY: 0.679 AC XY: 50433 AN XY: 74298

African (AFR) AF: 0.375 AC: 15534 AN: 41378

American (AMR) AF: 0.806 AC: 12327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2791 AN: 3468

East Asian (EAS) AF: 0.838 AC: 4345 AN: 5182

South Asian (SAS) AF: 0.730 AC: 3514 AN: 4814

European-Finnish (FIN) AF: 0.815 AC: 8610 AN: 10564

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52526 AN: 67976

Other (OTH) AF: 0.699 AC: 1478 AN: 2114

Alfa AF: 0.756 Hom.: 24190

Bravo AF: 0.663

TwinsUK AF: 0.761 AC: 2821

ALSPAC AF: 0.778 AC: 2997

ESP6500AA AF: 0.384 AC: 1693

ESP6500EA AF: 0.768 AC: 6603

ExAC AF: 0.756 AC: 91797

Asia WGS AF: 0.751 AC: 2612 AN: 3478

EpiCase AF: 0.780

EpiControl AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.44	.;T
MetaRNN	Benign	9.0e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.076	T;T
Polyphen		0.99	D;D
Vest4		0.063
MPC		0.53
ClinPred		0.011	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3750898; hg19: chr10-115609915; COSMIC: COSV107464332; COSMIC: COSV107464332;