chr11-71441212-C-T

Position:

chr11-71441212-C-T

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

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]

DHCR7 links:

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	Effect	MANE	Protein
DHCR7	NM_001360.3 linkuse as main transcript	c.626+15G>A	intron_variant	ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2 linkuse as main transcript	c.626+15G>A	intron_variant		NP_001157289.1
DHCR7	XM_011544777.3 linkuse as main transcript	c.626+15G>A	intron_variant		XP_011543079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 linkuse as main transcript	c.626+15G>A		intron_variant		1	NM_001360.3	ENSP00000347717	P1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46943

AN:

151958

Hom.:

7980

Cov.:

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.:

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.:

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 submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2018	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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) . -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Smith-Lemli-Opitz syndrome

Benign:5

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 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 provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over