rs971173

chr1-113905292-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000650596.1(DCLRE1B):c.-295G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 406,054 control chromosomes in the GnomAD database, including 29,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (15496 hom., cov: 33)
  • Exomes 𝑓: 0.31 (13763 hom.)
• Consequence: DCLRE1B ENST00000650596.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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]

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-113905292-G-T is Benign according to our data. Variant chr1-113905292-G-T is described in ClinVar as [Benign]. Clinvar id is 1259443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLRE1B	NM_022836.4			upstream_gene_variant		ENST00000650450.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLRE1B	ENST00000650450.2			upstream_gene_variant			NM_022836.4	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61852 AN: 151910 Hom.: 15466 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.310 AC: 78818 AN: 254026 Hom.: 13763 Cov.: 2 AF XY: 0.309 AC XY: 40941 AN XY: 132406

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.0965

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.407 AC: 61932 AN: 152028 Hom.: 15496 Cov.: 33 AF XY: 0.399 AC XY: 29642 AN XY: 74300

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.375

Alfa AF: 0.345 Hom.: 5675

Bravo AF: 0.414

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	17
Dann	Benign	0.90

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: rs971173; hg19: chr1-114447914; COSMIC: COSV56724812; COSMIC: COSV56724812;