1-113908685-C-T

Variant names:

• chr1-113908685-C-T
• rs1217390
• NM_022836.4:c.538+494C>T

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+494C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,080 control chromosomes in the GnomAD database, including 31,002 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 0.63 (31002 hom., cov: 32)
• Consequence: DCLRE1B NM_022836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 15 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1B	NM_022836.4	MANE Select	c.538+494C>T		intron	N/A	NP_073747.1	Q9H816
	DCLRE1B	NM_001363690.2		c.538+494C>T		intron	N/A	NP_001350619.1
	DCLRE1B	NM_001319946.2		c.160+494C>T		intron	N/A	NP_001306875.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1B	ENST00000650450.2	MANE Select	c.538+494C>T		intron	N/A	ENSP00000498042.1	Q9H816
	DCLRE1B	ENST00000466480.2	TSL:1	n.*153+494C>T		intron	N/A	ENSP00000497696.1	A0A3B3IT16
	DCLRE1B	ENST00000970516.1		c.538+494C>T		intron	N/A	ENSP00000640575.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96371 AN: 151962 Hom.: 30984 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.634 AC: 96432 AN: 152080 Hom.: 31002 Cov.: 32 AF XY: 0.630 AC XY: 46852 AN XY: 74314

African (AFR) AF: 0.744 AC: 30857 AN: 41492

American (AMR) AF: 0.569 AC: 8701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3472

East Asian (EAS) AF: 0.697 AC: 3610 AN: 5178

South Asian (SAS) AF: 0.492 AC: 2374 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6612 AN: 10530

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.591 AC: 40159 AN: 67984

Other (OTH) AF: 0.606 AC: 1280 AN: 2112

Alfa AF: 0.596 Hom.: 44847

Bravo AF: 0.639

Asia WGS AF: 0.564 AC: 1960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.26
PhyloP100		0.084
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: rs1217390; hg19: chr1-114451307;