rs111033327
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004004.6(GJB2):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,611,446 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004004.6 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000486 AC: 74AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000538 AC: 133AN: 247376Hom.: 0 AF XY: 0.000609 AC XY: 82AN XY: 134560
GnomAD4 exome AF: 0.000383 AC: 559AN: 1459134Hom.: 0 Cov.: 31 AF XY: 0.000355 AC XY: 258AN XY: 726018
GnomAD4 genome AF: 0.000486 AC: 74AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74484
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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This variant is associated with the following publications: (PMID: 20022641, 17666888, 22567369, 15744158, 17041943) -
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Autosomal recessive nonsyndromic hearing loss 1A Uncertain:2Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
not specified Benign:2
The *1C>T variant was identified in the 3?UTR of GJB2. This variant is located 1 base after the termination codon. Although, this variant has been detected in i ndividuals with hearing loss, it has never been identified with a second pathoge nic GJB2 variant (Frei 2005, Samanich 2007, Tang 2006, Rabionet unpublished). In addition, it was identified at an equal frequency (0.5%) in control chromosomes (Samanich 2007). In summary, the *1C>T variant is not expected to have clinical or pathological significance because it is not predicted to affect the transcri pt and has been found at an equal frequency in controls. -
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Ichthyosis, hystrix-like, with hearing loss Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Nonsyndromic genetic hearing loss Benign:1
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.*1C>T variant in GJB2 gene is 0,16% in latino population (72/35366 alleles with 95%CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which meets the BS1_Supporting rule. Bening computational veredict prediction from DANN and CADD predictors applying for BP4 rule. In summary, the c.*1C>T variant meets criteria to be classified likely benign (BS1_Supporting, BP4) -
Autosomal dominant nonsyndromic hearing loss 3A Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
GJB2-related disorder Benign:1
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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at