rs74909468
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001360.3(DHCR7):c.570C>T(p.Ala190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,208 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A190A) has been classified as Likely benign.
Frequency
Consequence
NM_001360.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHCR7 | NM_001360.3 | c.570C>T | p.Ala190= | synonymous_variant | 6/9 | ENST00000355527.8 | |
DHCR7 | NM_001163817.2 | c.570C>T | p.Ala190= | synonymous_variant | 6/9 | ||
DHCR7 | XM_011544777.3 | c.570C>T | p.Ala190= | synonymous_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHCR7 | ENST00000355527.8 | c.570C>T | p.Ala190= | synonymous_variant | 6/9 | 1 | NM_001360.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0101 AC: 1539AN: 152206Hom.: 27 Cov.: 33
GnomAD3 exomes AF: 0.00258 AC: 647AN: 250524Hom.: 10 AF XY: 0.00189 AC XY: 256AN XY: 135522
GnomAD4 exome AF: 0.00102 AC: 1489AN: 1461884Hom.: 25 Cov.: 34 AF XY: 0.000864 AC XY: 628AN XY: 727242
GnomAD4 genome AF: 0.0103 AC: 1574AN: 152324Hom.: 34 Cov.: 33 AF XY: 0.0104 AC XY: 771AN XY: 74486
ClinVar
Submissions by phenotype
Smith-Lemli-Opitz syndrome Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 05, 2017 | - - |
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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 29, 2018 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 11, 2017 | Variant summary: The DHCR7 c.570C>T (p.Ala190Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was found in the control population dataset of ExAC in 389/121388 control chromosomes (5 homozygotes) at a frequency of 0.0032046 and in gnomAD in 941/276256 control chromosomes (15 homozygotes) at a frequency of 0.003406, which do not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301). One clinical diagnostic laboratory classified this variant as uncertain significance and a second one classified it as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2016 | 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. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 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