chr11-71435795-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001425112.1(DHCR7):c.1142C>T(p.Thr381Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,607,910 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001425112.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHCR7 | NM_001360.3 | c.1008C>T | p.His336His | synonymous_variant | 9/9 | ENST00000355527.8 | NP_001351.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00540 AC: 822AN: 152246Hom.: 19 Cov.: 35
GnomAD3 exomes AF: 0.00876 AC: 2141AN: 244518Hom.: 49 AF XY: 0.00740 AC XY: 987AN XY: 133452
GnomAD4 exome AF: 0.00314 AC: 4566AN: 1455546Hom.: 133 Cov.: 37 AF XY: 0.00298 AC XY: 2153AN XY: 723118
GnomAD4 genome AF: 0.00538 AC: 819AN: 152364Hom.: 19 Cov.: 35 AF XY: 0.00616 AC XY: 459AN XY: 74514
ClinVar
Submissions by phenotype
Smith-Lemli-Opitz syndrome Benign:5
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 16, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 27, 2017 | Variant summary: The DHCR7 c.1008C>T (p.His336His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 889/113020 control chromosomes from ExAC (including 28 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.066619 (558/8376). This frequency is about 15 times the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. At least one clinical diagnostic laboratory in ClinVar has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as Benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 14, 2014 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2016 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at