NM_001360.3:c.231C>G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001360.3(DHCR7):c.231C>G(p.Thr77Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T77T) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DHCR7
NM_001360.3 synonymous
NM_001360.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.98
Publications
24 publications found
Genes affected
DHCR7 (HGNC:2860): (7-dehydrocholesterol reductase) This gene encodes an enzyme that removes the C(7-8) double bond in the B ring of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol. This gene is ubiquitously expressed and its transmembrane protein localizes to the endoplasmic reticulum membrane and nuclear outer membrane. Mutations in this gene cause Smith-Lemli-Opitz syndrome (SLOS); a syndrome that is metabolically characterized by reduced serum cholesterol levels and elevated serum 7-dehydrocholesterol levels and phenotypically characterized by cognitive disability, facial dysmorphism, syndactyly of second and third toes, and holoprosencephaly in severe cases to minimal physical abnormalities and near-normal intelligence in mild cases. Alternative splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Aug 2009]
DHCR7 Gene-Disease associations (from GenCC):
- Smith-Lemli-Opitz syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, ClinGen, Orphanet, Laboratory for Molecular Medicine
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 11-71444083-G-C is Benign according to our data. Variant chr11-71444083-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 882834.
BP7
Synonymous conserved (PhyloP=-3.98 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001360.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DHCR7 | NM_001360.3 | MANE Select | c.231C>G | p.Thr77Thr | synonymous | Exon 4 of 9 | NP_001351.2 | A0A024R5F7 | |
| DHCR7 | NM_001425107.1 | c.231C>G | p.Thr77Thr | synonymous | Exon 4 of 10 | NP_001412036.1 | A0A804HI25 | ||
| DHCR7 | NM_001425108.1 | c.231C>G | p.Thr77Thr | synonymous | Exon 4 of 9 | NP_001412037.1 | A0A804HJQ7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DHCR7 | ENST00000355527.8 | TSL:1 MANE Select | c.231C>G | p.Thr77Thr | synonymous | Exon 4 of 9 | ENSP00000347717.4 | Q9UBM7 | |
| DHCR7 | ENST00000407721.6 | TSL:1 | c.231C>G | p.Thr77Thr | synonymous | Exon 4 of 9 | ENSP00000384739.2 | Q9UBM7 | |
| DHCR7 | ENST00000685320.1 | c.-333-22C>G | intron | N/A | ENSP00000509319.1 | B4E1K5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461104Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726744 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461104
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726744
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44632
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26114
East Asian (EAS)
AF:
AC:
0
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
86046
European-Finnish (FIN)
AF:
AC:
0
AN:
53306
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111722
Other (OTH)
AF:
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
1
Smith-Lemli-Opitz syndrome (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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