rs1217390

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-113908685-C-G
• chr1-113908685-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022836.4(DCLRE1B):​c.538+494C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>G		intron	N/A	NP_073747.1	Q9H816
	DCLRE1B	NM_001363690.2		c.538+494C>G		intron	N/A	NP_001350619.1
	DCLRE1B	NM_001319946.2		c.160+494C>G		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>G		intron	N/A	ENSP00000498042.1	Q9H816
	DCLRE1B	ENST00000466480.2	TSL:1	n.*153+494C>G		intron	N/A	ENSP00000497696.1	A0A3B3IT16
	DCLRE1B	ENST00000970516.1		c.538+494C>G		intron	N/A	ENSP00000640575.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		0.084

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;