chr1-113905767-C-T

Position:

• chr1-113905767-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.69

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]

ACMG classification

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	Protein	UniProt
DCLRE1B	NM_022836.4	c.181C>T	p.His61Tyr	missense_variant	1/4	ENST00000650450.2	NP_073747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1B	ENST00000650450.2	c.181C>T	p.His61Tyr	missense_variant	1/4		NM_022836.4	ENSP00000498042	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24503 AN: 152076 Hom.: 2957 Cov.: 32

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

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.: 32 AF XY: 0.183 AC XY: 132809 AN XY: 726224

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.: 32 AF XY: 0.166 AC XY: 12320 AN XY: 74394

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary spastic paraplegia 47 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 26, 2020

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.66	.;T;T
MetaRNN	Benign	0.00024	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.32	T
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	T
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

Other links and lift over

dbSNP: rs11552449; hg19: chr1-114448389; COSMIC: COSV56724332; COSMIC: COSV56724332;