rs73980038
Variant summary
Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_015681.6(B9D1):c.181C>T(p.Arg61Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,614,102 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_015681.6 missense
Scores
Clinical Significance
Conservation
Publications
- ciliopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Joubert syndrome 27Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Meckel syndrome, type 9Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Meckel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00981 AC: 1492AN: 152136Hom.: 24 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00260 AC: 653AN: 251442 AF XY: 0.00181 show subpopulations
GnomAD4 exome AF: 0.000993 AC: 1451AN: 1461850Hom.: 24 Cov.: 30 AF XY: 0.000846 AC XY: 615AN XY: 727224 show subpopulations
GnomAD4 genome AF: 0.00980 AC: 1492AN: 152252Hom.: 24 Cov.: 32 AF XY: 0.00939 AC XY: 699AN XY: 74448 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:2
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:1
- -
Meckel syndrome, type 9 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. -
Meckel-Gruber syndrome;C0431399:Joubert syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at