chr11-71444125-C-T

Position:

chr11-71444125-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000355527.8(DHCR7):c.189G>A(p.Gln63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,610,010 control chromosomes in the GnomAD database, including 392,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27496 hom., cov: 33)

Exomes 𝑓: 0.69 ( 364882 hom. )

Consequence

DHCR7
ENST00000355527.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 3.07

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-71444125-C-T is Benign according to our data. Variant chr11-71444125-C-T is described in ClinVar as [Benign]. Clinvar id is 93713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-71444125-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DHCR7	NM_001360.3 linkuse as main transcript	c.189G>A	p.Gln63=	synonymous_variant	4/9	ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2 linkuse as main transcript	c.189G>A	p.Gln63=	synonymous_variant	4/9		NP_001157289.1
DHCR7	XM_011544777.3 linkuse as main transcript	c.189G>A	p.Gln63=	synonymous_variant	4/9		XP_011543079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 linkuse as main transcript	c.189G>A	p.Gln63=	synonymous_variant	4/9	1	NM_001360.3	ENSP00000347717	P1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87821

AN:

151986

Hom.:

27466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.458

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.565

AC:

137936

AN:

243970

Hom.:

42951

AF XY:

0.558

AC XY:

73683

AN XY:

131994

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.688

AC:

1002927

AN:

1457908

Hom.:

364882

Cov.:

AF XY:

0.674

AC XY:

488636

AN XY:

724926

show subpopulations

Gnomad4 AFR exome

AF:

0.373

Gnomad4 AMR exome

AF:

0.539

Gnomad4 ASJ exome

AF:

0.626

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.635

GnomAD4 genome

AF:

0.578

AC:

87896

AN:

152102

Hom.:

27496

Cov.:

AF XY:

0.562

AC XY:

41785

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.548

Alfa

AF:

0.676

Hom.:

18521

Bravo

AF:

0.578

Asia WGS

AF:

0.265

AC:

925

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Smith-Lemli-Opitz syndrome

Benign:6

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Aug 09, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 08, 2017	- -

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2018	- -

not provided

Benign:2

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

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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