rs12046289

Variant names:

• chr1-113908764-G-A
• rs12046289
• NM_022836.4:c.538+573G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 8

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1B	NM_022836.4	MANE Select	c.538+573G>A		intron	N/A	NP_073747.1
	DCLRE1B	NM_001363690.2		c.538+573G>A		intron	N/A	NP_001350619.1
	DCLRE1B	NM_001319946.2		c.160+573G>A		intron	N/A	NP_001306875.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1B	ENST00000650450.2	MANE Select	c.538+573G>A		intron	N/A	ENSP00000498042.1
	DCLRE1B	ENST00000466480.2	TSL:1	n.*153+573G>A		intron	N/A	ENSP00000497696.1
	DCLRE1B	ENST00000650596.1		c.355+1603G>A		intron	N/A	ENSP00000497882.1

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

African (AFR) AF: 0.0364 AC: 1502 AN: 41310

American (AMR) AF: 0.281 AC: 4290 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2644 AN: 5170

South Asian (SAS) AF: 0.143 AC: 689 AN: 4810

European-Finnish (FIN) AF: 0.139 AC: 1453 AN: 10478

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9094 AN: 67968

Other (OTH) AF: 0.161 AC: 339 AN: 2106

Alfa AF: 0.135 Hom.: 2158

Bravo AF: 0.149

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.53
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12046289; hg19: chr1-114451386;