rs736894

Variant names:

• chr11-71441212-C-T
• rs736894
• NM_001360.3:c.626+15G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.534

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]

ACMG classification

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 rank	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.626+15G>A		intron_variant	Intron 6 of 8	ENST00000355527.8	NP_001351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.626+15G>A		intron_variant	Intron 6 of 8	1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320.1	c.41+15G>A		intron_variant	Intron 5 of 7			ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46943 AN: 151958 Hom.: 7980 Cov.: 33

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

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

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

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

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 06, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.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) . -

Smith-Lemli-Opitz syndrome Benign:5

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Oct 05, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

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