rs146867923
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The ENST00000355527.8(DHCR7):c.70G>T(p.Ala24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,614,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A24E) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000355527.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHCR7 | NM_001360.3 | c.70G>T | p.Ala24Ser | missense_variant | 3/9 | ENST00000355527.8 | NP_001351.2 | |
DHCR7 | NM_001163817.2 | c.70G>T | p.Ala24Ser | missense_variant | 3/9 | NP_001157289.1 | ||
DHCR7 | XM_011544777.3 | c.70G>T | p.Ala24Ser | missense_variant | 3/9 | XP_011543079.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHCR7 | ENST00000355527.8 | c.70G>T | p.Ala24Ser | missense_variant | 3/9 | 1 | NM_001360.3 | ENSP00000347717 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00219 AC: 334AN: 152204Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000553 AC: 139AN: 251496Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135922
GnomAD4 exome AF: 0.000233 AC: 340AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.000180 AC XY: 131AN XY: 727244
GnomAD4 genome AF: 0.00221 AC: 337AN: 152322Hom.: 1 Cov.: 33 AF XY: 0.00219 AC XY: 163AN XY: 74482
ClinVar
Submissions by phenotype
Smith-Lemli-Opitz syndrome Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 05, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 18, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 01, 2016 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 29, 2020 | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | DHCR7: BS2 - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 07, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
DHCR7-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 20, 2020 | 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