11-71441212-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 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 -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 VariationId is 93721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	c.626+15G>A		intron_variant	Intron 6 of 8	ENST00000355527.8	NP_001351.2	Q9UBM7A0A024R5F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 link	c.626+15G>A		intron_variant	Intron 6 of 8	1	NM_001360.3	ENSP00000347717.4		Q9UBM7
DHCR7	ENST00000685320.1 link	c.41+15G>A		intron_variant	Intron 5 of 7			ENSP00000509319.1		B4E1K5

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

GnomAD2 exomes

AF:

0.298

AC:

74170

AN:

249116

AF XY:

0.304

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 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

African (AFR)

AF:

0.440

AC:

14718

AN:

33456

American (AMR)

AF:

0.215

AC:

9614

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

5762

AN:

26134

East Asian (EAS)

AF:

0.464

AC:

18404

AN:

39694

South Asian (SAS)

AF:

0.471

AC:

40596

AN:

86228

European-Finnish (FIN)

AF:

0.358

AC:

19110

AN:

53384

Middle Eastern (MID)

AF:

0.333

AC:

1917

AN:

5758

European-Non Finnish (NFE)

AF:

0.196

AC:

218336

AN:

1111218

Other (OTH)

AF:

0.259

AC:

15644

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

13067

26134

39200

52267

65334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7582

15164

22746

30328

37910

<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:

0.309

AC:

46952

AN:

152076

Hom.:

7983

Cov.:

AF XY:

0.320

AC XY:

23794

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.420

AC:

17417

AN:

41452

American (AMR)

AF:

0.284

AC:

4347

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

761

AN:

3472

East Asian (EAS)

AF:

0.412

AC:

2125

AN:

5158

South Asian (SAS)

AF:

0.471

AC:

2271

AN:

4824

European-Finnish (FIN)

AF:

0.376

AC:

3982

AN:

10582

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.220

AC:

14940

AN:

67988

Other (OTH)

AF:

0.337

AC:

712

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1646

3292

4939

6585

8231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.274

Hom.:

1793

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

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) . -

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

- -

Smith-Lemli-Opitz syndrome

Benign:5

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

- -

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

- -

Jul 01, 2021

Genome-Nilou Lab

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

(source)

DANN

Benign

0.83

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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