chr1-34761437-C-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_153212.3(GJB4):c.183C>A(p.Pro61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,614,148 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 66 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 61 hom. )
Consequence
GJB4
NM_153212.3 synonymous
NM_153212.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.380
Genes affected
GJB4 (HGNC:4286): (gap junction protein beta 4) This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 1-34761437-C-A is Benign according to our data. Variant chr1-34761437-C-A is described in ClinVar as [Benign]. Clinvar id is 791789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.38 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB4 | NM_153212.3 | c.183C>A | p.Pro61= | synonymous_variant | 2/2 | ENST00000339480.3 | |
GJB4 | XM_011540679.3 | c.183C>A | p.Pro61= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB4 | ENST00000339480.3 | c.183C>A | p.Pro61= | synonymous_variant | 2/2 | 2 | NM_153212.3 | P1 | |
ENST00000542839.1 | n.549G>T | non_coding_transcript_exon_variant | 2/2 | 5 | |||||
SMIM12 | ENST00000426886.1 | c.208-43028G>T | intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0152 AC: 2321AN: 152210Hom.: 66 Cov.: 33
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GnomAD3 exomes AF: 0.00399 AC: 1001AN: 251024Hom.: 33 AF XY: 0.00279 AC XY: 378AN XY: 135694
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GnomAD4 exome AF: 0.00158 AC: 2305AN: 1461820Hom.: 61 Cov.: 31 AF XY: 0.00134 AC XY: 971AN XY: 727202
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GnomAD4 genome ? AF: 0.0153 AC: 2325AN: 152328Hom.: 66 Cov.: 33 AF XY: 0.0149 AC XY: 1108AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
GJB4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2020 | 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). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at