20-49374193-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 1P and 18B. PP2BP4_ModerateBP6_Very_StrongBS1BS2
The NM_004975.4(KCNB1):c.1367G>A(p.Arg456Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R456G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004975.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.1367G>A | p.Arg456Gln | missense_variant | 2/2 | ENST00000371741.6 | |
LOC105372649 | XR_001754659.2 | n.1201+42169C>T | intron_variant, non_coding_transcript_variant | ||||
KCNB1 | XM_011528799.3 | c.1367G>A | p.Arg456Gln | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.1367G>A | p.Arg456Gln | missense_variant | 2/2 | 1 | NM_004975.4 | P1 | |
KCNB1 | ENST00000635465.1 | c.1367G>A | p.Arg456Gln | missense_variant | 3/3 | 1 | P1 | ||
ENST00000637341.1 | n.206+42169C>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
KCNB1 | ENST00000635878.1 | c.97-74810G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251384Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135850
GnomAD4 exome AF: 0.000226 AC: 331AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 166AN XY: 727222
GnomAD4 genome AF: 0.000112 AC: 17AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74350
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | KCNB1: BP5, BS1:Supporting - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2021 | - - |
Developmental and epileptic encephalopathy, 26 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
KCNB1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 20, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at