9-114426329-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001083885.3(WHRN):c.-102C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000259 in 1,613,976 control chromosomes in the GnomAD database, including 3 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
Consequence
NM_001083885.3 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00132 AC: 201AN: 152200Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000355 AC: 89AN: 250870Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135632
GnomAD4 exome AF: 0.000145 AC: 212AN: 1461658Hom.: 1 Cov.: 30 AF XY: 0.000116 AC XY: 84AN XY: 727128
GnomAD4 genome AF: 0.00135 AC: 206AN: 152318Hom.: 2 Cov.: 33 AF XY: 0.00126 AC XY: 94AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
The p.Arg350Trp variant (rs142990800) has been reported in the medical literature in a single Egyptian individual with Usher syndrome (Aller 2010); however, inheritance and specific clinical information were not reported for this individual. The p.Arg350Trp variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.53% in the African population (identified in 128 out of 23,990 chromosomes; 1 homozygote), and is classified as likely benign in ClinVar (Variant ID: 178337). The arginine at codon 350 is moderately conserved considering 12 species (Alamut software v2.9.0), but computational analyses suggest that this variant affects the WHRN protein structure/function (SIFT: damaging, PolyPhen2: possibly damaging, MutationTaster: disease causing). While this variant appears to be a benign polymorphism in the African population, the available evidence is insufficient to classify the clinical significance of this variant with certainty. -
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This variant is associated with the following publications: (PMID: 20352026, 30245029) -
not specified Benign:1
Arg350Trp in Exon 04 of DFNB31: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (16/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs142990800). -
WHRN-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