11-118141320-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_ModerateBP6_ModerateBS2
The NM_174934.4(SCN4B):c.480C>G(p.Asn160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,108 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 (★). Synonymous variant affecting the same amino acid position (i.e. N160N) has been classified as Likely benign.
Frequency
Consequence
NM_174934.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4B | NM_174934.4 | c.480C>G | p.Asn160Lys | missense_variant | 4/5 | ENST00000324727.9 | |
SCN4B | NM_001142349.2 | c.150C>G | p.Asn50Lys | missense_variant | 3/4 | ||
SCN4B | NM_001142348.2 | c.78C>G | p.Asn26Lys | missense_variant | 2/3 | ||
SCN4B | NR_024527.2 | n.469C>G | non_coding_transcript_exon_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4B | ENST00000324727.9 | c.480C>G | p.Asn160Lys | missense_variant | 4/5 | 1 | NM_174934.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251412Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135872
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460108Hom.: 0 Cov.: 33 AF XY: 0.00000964 AC XY: 7AN XY: 726368
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 15, 2021 | Variant summary: SCN4B c.480C>G (p.Asn160Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-05 in 251412 control chromosomes, predominantly at a frequency of 0.0004 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 136 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN4B causing Long QT Syndrome phenotype (2.9e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.480C>G in individuals affected with Long QT Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at