rs12046289

Positions:

• chr1-113908764-G-A
• chr1-113908764-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022836.4(DCLRE1B):​c.538+573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,778 control chromosomes in the GnomAD database, including 2,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2191 hom., cov: 33)
• Consequence: DCLRE1B NM_022836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLRE1B	NM_022836.4	c.538+573G>A		intron_variant		ENST00000650450.2	NP_073747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLRE1B	ENST00000650450.2	c.538+573G>A		intron_variant			NM_022836.4	ENSP00000498042	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20618 AN: 151660 Hom.: 2199 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20601 AN: 151778 Hom.: 2191 Cov.: 33 AF XY: 0.141 AC XY: 10435 AN XY: 74142

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.161

Alfa AF: 0.135 Hom.: 674

Bravo AF: 0.149

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.53

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: rs12046289; hg19: chr1-114451386;