rs736894

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001360.3(DHCR7):​c.626+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,613,024 control chromosomes in the GnomAD database, including 55,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7983 hom., cov: 33)
Exomes 𝑓: 0.24 ( 47170 hom. )

Consequence

DHCR7
NM_001360.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.534
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 11-71441212-C-T is Benign according to our data. Variant chr11-71441212-C-T is described in ClinVar as [Benign]. Clinvar id is 93721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-71441212-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DHCR7NM_001360.3 linkuse as main transcriptc.626+15G>A intron_variant ENST00000355527.8 NP_001351.2
DHCR7NM_001163817.2 linkuse as main transcriptc.626+15G>A intron_variant NP_001157289.1
DHCR7XM_011544777.3 linkuse as main transcriptc.626+15G>A intron_variant XP_011543079.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHCR7ENST00000355527.8 linkuse as main transcriptc.626+15G>A intron_variant 1 NM_001360.3 ENSP00000347717 P1

Frequencies

GnomAD3 genomes
AF:
0.309
AC:
46943
AN:
151958
Hom.:
7980
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.421
Gnomad AMI
AF:
0.326
Gnomad AMR
AF:
0.285
Gnomad ASJ
AF:
0.219
Gnomad EAS
AF:
0.411
Gnomad SAS
AF:
0.473
Gnomad FIN
AF:
0.376
Gnomad MID
AF:
0.363
Gnomad NFE
AF:
0.220
Gnomad OTH
AF:
0.334
GnomAD3 exomes
AF:
0.298
AC:
74170
AN:
249116
Hom.:
12396
AF XY:
0.304
AC XY:
40978
AN XY:
134828
show subpopulations
Gnomad AFR exome
AF:
0.427
Gnomad AMR exome
AF:
0.208
Gnomad ASJ exome
AF:
0.223
Gnomad EAS exome
AF:
0.411
Gnomad SAS exome
AF:
0.470
Gnomad FIN exome
AF:
0.366
Gnomad NFE exome
AF:
0.235
Gnomad OTH exome
AF:
0.281
GnomAD4 exome
AF:
0.236
AC:
344101
AN:
1460948
Hom.:
47170
Cov.:
32
AF XY:
0.243
AC XY:
176757
AN XY:
726836
show subpopulations
Gnomad4 AFR exome
AF:
0.440
Gnomad4 AMR exome
AF:
0.215
Gnomad4 ASJ exome
AF:
0.220
Gnomad4 EAS exome
AF:
0.464
Gnomad4 SAS exome
AF:
0.471
Gnomad4 FIN exome
AF:
0.358
Gnomad4 NFE exome
AF:
0.196
Gnomad4 OTH exome
AF:
0.259
GnomAD4 genome
AF:
0.309
AC:
46952
AN:
152076
Hom.:
7983
Cov.:
33
AF XY:
0.320
AC XY:
23794
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.420
Gnomad4 AMR
AF:
0.284
Gnomad4 ASJ
AF:
0.219
Gnomad4 EAS
AF:
0.412
Gnomad4 SAS
AF:
0.471
Gnomad4 FIN
AF:
0.376
Gnomad4 NFE
AF:
0.220
Gnomad4 OTH
AF:
0.337
Alfa
AF:
0.271
Hom.:
1732
Bravo
AF:
0.299
Asia WGS
AF:
0.395
AC:
1370
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jun 06, 2018- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 21, 2016c.626+15G>A in intron 6 of DHCR7: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 47.31% (7809/16506) of South Asian chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs736894) . -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Smith-Lemli-Opitz syndrome Benign:5
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 01, 2021- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 05, 2021- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.7
DANN
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs736894; hg19: chr11-71152258; COSMIC: COSV62796127; COSMIC: COSV62796127; API