Variant 1-113907040-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022836.4(DCLRE1B):c.234T>C(p.His78His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,556 control chromosomes in the GnomAD database, including 33,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2965 hom., cov: 30)

Exomes 𝑓: 0.19 ( 30628 hom. )

Consequence

DCLRE1B
NM_022836.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.133

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-113907040-T-C is Benign according to our data. Variant chr1-113907040-T-C is described in ClinVar as [Benign]. Clinvar id is 1169794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.133 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1B	NM_022836.4 linkuse as main transcript	c.234T>C	p.His78His	synonymous_variant	2/4	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.234T>C	p.His78His	synonymous_variant	2/4		NM_022836.4	ENSP00000498042.1		Q9H816

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24537

AN:

151616

Hom.:

2973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.123

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:

0.224

AC:

56379

AN:

251464

Hom.:

9268

AF XY:

0.213

AC XY:

28902

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.593

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:

0.186

AC:

271656

AN:

1461824

Hom.:

30628

Cov.:

AF XY:

0.183

AC XY:

133407

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0341

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.562

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.162

AC:

24526

AN:

151732

Hom.:

2965

Cov.:

AF XY:

0.166

AC XY:

12333

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.0389

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.123

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:

0.156

Hom.:

2813

Bravo

AF:

0.173

Asia WGS

AF:

0.318

AC:

1102

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.164

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

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. -

Hoyeraal-Hreidarsson syndrome;C3502105:Autosomal recessive dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.6

DANN

Benign

0.69

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

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