Variant 1-113905767-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022836.4(DCLRE1B):c.181C>T(p.His61Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.183 in 1,612,434 control chromosomes in the GnomAD database, including 33,388 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2950 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30438 hom. )

Consequence

DCLRE1B
NM_022836.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]

DCLRE1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.374649E-4).

BP6

Variant 1-113905767-C-T is Benign according to our data. Variant chr1-113905767-C-T is described in ClinVar as [Benign]. Clinvar id is 225770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLRE1B	NM_022836.4 linkuse as main transcript	c.181C>T	p.His61Tyr	missense_variant	1/4	ENST00000650450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLRE1B	ENST00000650450.2 linkuse as main transcript	c.181C>T	p.His61Tyr	missense_variant	1/4		NM_022836.4	P1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24503

AN:

152076

Hom.:

2957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.223

AC:

55284

AN:

247452

Hom.:

9062

AF XY:

0.212

AC XY:

28374

AN XY:

133948

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.592

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.185

AC:

270551

AN:

1460240

Hom.:

30438

Cov.:

AF XY:

0.183

AC XY:

132809

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.161

AC:

24493

AN:

152194

Hom.:

2950

Cov.:

AF XY:

0.166

AC XY:

12320

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0390

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.181

Hom.:

5667

Bravo

AF:

0.172

TwinsUK

AF:

0.173

AC:

641

ALSPAC

AF:

0.175

AC:

675

ESP6500AA

AF:

0.0420

AC:

185

ESP6500EA

AF:

0.174

AC:

1495

ExAC

AF:

0.211

AC:

25585

Asia WGS

AF:

0.317

AC:

1101

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.163

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Hereditary spastic paraplegia 47

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 26, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.062

T;.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.66

.;T;T

MetaRNN

Benign

0.00024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.61

N;.;.

REVEL

Benign

0.17

Sift

Benign

0.49

T;.;.

Sift4G

Benign

0.15

T;.;.

Polyphen

0.14

B;.;B

Vest4

0.047

MPC

0.20

ClinPred

0.018

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.092

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over