Variant 1-113911976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022836.4(DCLRE1B):c.1384G>A(p.Asp462Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,614,206 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 52 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 30 hom. )

Consequence

DCLRE1B
NM_022836.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.155

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:

DCLRE1B (HGNC:):

DCLRE1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022997558).

BP6

Variant 1-113911976-G-A is Benign according to our data. Variant chr1-113911976-G-A is described in ClinVar as [Benign]. Clinvar id is 533712.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2077/152328) while in subpopulation AFR AF= 0.0476 (1979/41560). AF 95% confidence interval is 0.0459. There are 52 homozygotes in gnomad4. There are 1008 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1B	NM_022836.4 linkuse as main transcript	c.1384G>A	p.Asp462Asn	missense_variant	4/4	ENST00000650450.2	NP_073747.1	Q9H816

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1B	ENST00000650450.2 linkuse as main transcript	c.1384G>A	p.Asp462Asn	missense_variant	4/4		NM_022836.4	ENSP00000498042.1		Q9H816

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2066

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0475

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00352

AC:

885

AN:

251430

Hom.:

AF XY:

0.00236

AC XY:

321

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00127

AC:

1861

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

778

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.0136

AC:

2077

AN:

152328

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1008

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0476

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00530

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00448

AC:

544

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hoyeraal-Hreidarsson syndrome;C3502105:Autosomal recessive dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.49

.;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.22

N;.;.

REVEL

Benign

0.064

Sift

Benign

0.37

T;.;.

Sift4G

Benign

0.24

T;.;.

Polyphen

0.0

B;.;B

Vest4

0.073

MVP

0.37

MPC

0.15

ClinPred

0.0030

GERP RS

1.9

Varity_R

0.021

gMVP

0.12

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