11-71444125-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001360.3(DHCR7):c.189G>A(p.Gln63Gln) 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
NM_001360.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.07

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

Smith-Lemli-Opitz syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)

DHCR7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 93713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DHCR7	NM_001360.3 link	c.189G>A	p.Gln63Gln	synonymous_variant	Exon 4 of 9	ENST00000355527.8	NP_001351.2	Q9UBM7A0A024R5F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 link	c.189G>A	p.Gln63Gln	synonymous_variant	Exon 4 of 9	1	NM_001360.3	ENSP00000347717.4		Q9UBM7
DHCR7	ENST00000685320.1 link	c.-333-64G>A		intron_variant	Intron 2 of 7			ENSP00000509319.1		B4E1K5

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

GnomAD2 exomes

AF:

0.565

AC:

137936

AN:

243970

AF XY:

0.558

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 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

African (AFR)

AF:

0.373

AC:

12489

AN:

33438

American (AMR)

AF:

0.539

AC:

23709

AN:

43964

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

16335

AN:

26076

East Asian (EAS)

AF:

0.333

AC:

13174

AN:

39572

South Asian (SAS)

AF:

0.215

AC:

18444

AN:

85718

European-Finnish (FIN)

AF:

0.587

AC:

31052

AN:

52894

Middle Eastern (MID)

AF:

0.466

AC:

2684

AN:

5764

European-Non Finnish (NFE)

AF:

0.763

AC:

846811

AN:

1110252

Other (OTH)

AF:

0.635

AC:

38229

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

14876

29753

44629

59506

74382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20052

40104

60156

80208

100260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.578

AC:

87896

AN:

152102

Hom.:

27496

Cov.:

AF XY:

0.562

AC XY:

41785

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.404

AC:

16751

AN:

41472

American (AMR)

AF:

0.536

AC:

8199

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

2137

AN:

3468

East Asian (EAS)

AF:

0.365

AC:

1893

AN:

5182

South Asian (SAS)

AF:

0.203

AC:

977

AN:

4814

European-Finnish (FIN)

AF:

0.569

AC:

6027

AN:

10590

Middle Eastern (MID)

AF:

0.476

AC:

138

AN:

290

European-Non Finnish (NFE)

AF:

0.736

AC:

50006

AN:

67978

Other (OTH)

AF:

0.548

AC:

1156

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1743

3486

5229

6972

8715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.665

Hom.:

19070

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

Oct 05, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 09, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 12, 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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 08, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

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

- -

Inborn genetic diseases

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.84

PhyloP100

3.1

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over