rs727504755
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_004004.6(GJB2):c.219C>T(p.His73=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 1,461,852 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 (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
GJB2
NM_004004.6 synonymous
NM_004004.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 8.09
Genes affected
GJB2 (HGNC:4284): (gap junction protein beta 2) This gene encodes a member of the gap junction protein family. The gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels that facilitate the transfer of ions and small molecules between cells. The gap junction proteins, also known as connexins, purified from fractions of enriched gap junctions from different tissues differ. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene are responsible for as much as 50% of pre-lingual, recessive deafness. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 13-20189363-G-A is Benign according to our data. Variant chr13-20189363-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 179274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB2 | NM_004004.6 | c.219C>T | p.His73= | synonymous_variant | 2/2 | ENST00000382848.5 | |
GJB2 | XM_011535049.3 | c.219C>T | p.His73= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB2 | ENST00000382848.5 | c.219C>T | p.His73= | synonymous_variant | 2/2 | 1 | NM_004004.6 | P1 | |
GJB2 | ENST00000382844.2 | c.219C>T | p.His73= | synonymous_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251408Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461852Hom.: 0 Cov.: 33 AF XY: 0.0000426 AC XY: 31AN XY: 727224
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 10, 2013 | His73His in exon 2 of GJB2: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and it is not located wit hin the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2023 | - - |
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