1-113911939-G-C

Variant names:

• chr1-113911939-G-C
• NM_022836.4:c.1347G>C
• DCLRE1B p.Glu449Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022836.4(DCLRE1B):​c.1347G>C​(p.Glu449Asp) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCLRE1B NM_022836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• Publications: 0 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]

HIPK1-AS1 (HGNC:50576): (HIPK1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112966776).

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.1347G>C	p.Glu449Asp	missense	Exon 4 of 4	NP_073747.1	Q9H816
	DCLRE1B	NM_001319946.2		c.969G>C	p.Glu323Asp	missense	Exon 3 of 3	NP_001306875.1
	DCLRE1B	NM_001319947.2		c.969G>C	p.Glu323Asp	missense	Exon 4 of 4	NP_001306876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLRE1B	ENST00000650450.2	MANE Select	c.1347G>C	p.Glu449Asp	missense	Exon 4 of 4	ENSP00000498042.1	Q9H816
	DCLRE1B	ENST00000466480.2	TSL:1	n.*861+101G>C		intron	N/A	ENSP00000497696.1	A0A3B3IT16
	DCLRE1B	ENST00000970516.1		c.1347G>C	p.Glu449Asp	missense	Exon 5 of 5	ENSP00000640575.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.99
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.090
Sift	Uncertain	0.013	D
Sift4G	Benign	0.17	T
Varity_R		0.068
gMVP		0.14
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-114454561;