20-32800931-C-T
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006892.4(DNMT3B):c.1996+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,614,140 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006892.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- immunodeficiency-centromeric instability-facial anomalies syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
- facioscapulohumeral muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- immunodeficiency-centromeric instability-facial anomalies syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0180 AC: 2744AN: 152220Hom.: 73 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00483 AC: 1214AN: 251476 AF XY: 0.00359 show subpopulations
GnomAD4 exome AF: 0.00211 AC: 3086AN: 1461802Hom.: 74 Cov.: 35 AF XY: 0.00184 AC XY: 1336AN XY: 727212 show subpopulations
GnomAD4 genome AF: 0.0181 AC: 2761AN: 152338Hom.: 74 Cov.: 33 AF XY: 0.0173 AC XY: 1292AN XY: 74506 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:2
- -
- -
Immunodeficiency-centromeric instability-facial anomalies syndrome 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
DNMT3B-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at