11-71444107-A-G

Position:

chr11-71444107-A-G

Variant summary

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

The NM_001360.3(DHCR7):c.207T>C(p.Thr69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 1,612,316 control chromosomes in the GnomAD database, including 693,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61539 hom., cov: 33)

Exomes 𝑓: 0.93 ( 631854 hom. )

Consequence

DHCR7
NM_001360.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.42

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=-0.92).

BP6

Variant 11-71444107-A-G is Benign according to our data. Variant chr11-71444107-A-G is described in ClinVar as [Benign]. Clinvar id is 93715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-71444107-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 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.207T>C	p.Thr69=	synonymous_variant	4/9	ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2 linkuse as main transcript	c.207T>C	p.Thr69=	synonymous_variant	4/9		NP_001157289.1
DHCR7	XM_011544777.3 linkuse as main transcript	c.207T>C	p.Thr69=	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.207T>C	p.Thr69=	synonymous_variant	4/9	1	NM_001360.3	ENSP00000347717	P1

Frequencies

GnomAD3 genomes

AF:

0.896

AC:

136326

AN:

152110

Hom.:

61508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.839

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.846

Gnomad ASJ

AF:

0.839

Gnomad EAS

AF:

0.842

Gnomad SAS

AF:

0.679

Gnomad FIN

AF:

0.946

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.956

Gnomad OTH

AF:

0.896

GnomAD3 exomes

AF:

0.872

AC:

215917

AN:

247586

Hom.:

95461

AF XY:

0.870

AC XY:

116512

AN XY:

133990

show subpopulations

Gnomad AFR exome

AF:

0.837

Gnomad AMR exome

AF:

0.771

Gnomad ASJ exome

AF:

0.850

Gnomad EAS exome

AF:

0.849

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.946

Gnomad NFE exome

AF:

0.950

Gnomad OTH exome

AF:

0.888

GnomAD4 exome

AF:

0.927

AC:

1353425

AN:

1460088

Hom.:

631854

Cov.:

AF XY:

0.921

AC XY:

668479

AN XY:

726190

show subpopulations

Gnomad4 AFR exome

AF:

0.829

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.849

Gnomad4 EAS exome

AF:

0.868

Gnomad4 SAS exome

AF:

0.688

Gnomad4 FIN exome

AF:

0.945

Gnomad4 NFE exome

AF:

0.959

Gnomad4 OTH exome

AF:

0.901

GnomAD4 genome

AF:

0.896

AC:

136408

AN:

152228

Hom.:

61539

Cov.:

AF XY:

0.892

AC XY:

66388

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.839

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.839

Gnomad4 EAS

AF:

0.843

Gnomad4 SAS

AF:

0.679

Gnomad4 FIN

AF:

0.946

Gnomad4 NFE

AF:

0.956

Gnomad4 OTH

AF:

0.894

Alfa

AF:

0.929

Hom.:

76147

Bravo

AF:

0.888

Asia WGS

AF:

0.706

AC:

2456

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	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.	May 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 08, 2017	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 05, 2021	- -

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 16, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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. -

not provided

Benign:1

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

-0.92

CADD

Benign

0.061

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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