chr6-35805543-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182548.4(LHFPL5):c.-128C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 899,654 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0066 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 5 hom. )
Consequence
LHFPL5
NM_182548.4 5_prime_UTR
NM_182548.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.910
Genes affected
LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 6-35805543-C-T is Benign according to our data. Variant chr6-35805543-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 356484.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (999/152326) while in subpopulation AFR AF= 0.0233 (968/41584). AF 95% confidence interval is 0.0221. There are 12 homozygotes in gnomad4. There are 478 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LHFPL5 | NM_182548.4 | c.-128C>T | 5_prime_UTR_variant | 1/4 | ENST00000360215.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LHFPL5 | ENST00000360215.3 | c.-128C>T | 5_prime_UTR_variant | 1/4 | 1 | NM_182548.4 | P1 | ||
LHFPL5 | ENST00000651132.1 | c.-128C>T | 5_prime_UTR_variant | 4/7 | P1 | ||||
LHFPL5 | ENST00000651676.1 | c.-128C>T | 5_prime_UTR_variant | 1/4 | P1 | ||||
LHFPL5 | ENST00000651994.1 | c.-128C>T | 5_prime_UTR_variant, NMD_transcript_variant | 1/4 |
Frequencies
GnomAD3 genomes ? AF: 0.00655 AC: 997AN: 152208Hom.: 12 Cov.: 32
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GnomAD4 exome AF: 0.000781 AC: 584AN: 747328Hom.: 5 Cov.: 10 AF XY: 0.000618 AC XY: 241AN XY: 390260
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 67 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at