chr11-71443959-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001360.3(DHCR7):c.321+34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00901 in 1,569,252 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 611 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 504 hom. )

Consequence

DHCR7
NM_001360.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.74

Publications

0 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.03).

BP6

Variant 11-71443959-G-T is Benign according to our data. Variant chr11-71443959-G-T is described in ClinVar as Benign. ClinVar VariationId is 257965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHCR7	NM_001360.3 link	c.321+34C>A		intron_variant	Intron 4 of 8	ENST00000355527.8	NP_001351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8 link	c.321+34C>A		intron_variant	Intron 4 of 8	1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320.1 link	c.-265+34C>A		intron_variant	Intron 3 of 7			ENSP00000509319.1

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7347

AN:

152122

Hom.:

593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0108

AC:

2383

AN:

220338

AF XY:

0.00787

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000237

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000437

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00475

AC:

6734

AN:

1417012

Hom.:

504

Cov.:

AF XY:

0.00408

AC XY:

2870

AN XY:

703752

show subpopulations

African (AFR)

AF:

0.164

AC:

5372

AN:

32718

American (AMR)

AF:

0.00766

AC:

318

AN:

41508

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24906

East Asian (EAS)

AF:

0.000102

AC:

AN:

39098

South Asian (SAS)

AF:

0.000350

AC:

AN:

82752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51060

Middle Eastern (MID)

AF:

0.00899

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000283

AC:

306

AN:

1080526

Other (OTH)

AF:

0.0111

AC:

653

AN:

58770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

270

541

811

1082

1352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<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:

0.0487

AC:

7410

AN:

152240

Hom.:

611

Cov.:

AF XY:

0.0473

AC XY:

3519

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.169

AC:

7025

AN:

41536

American (AMR)

AF:

0.0176

AC:

270

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

67996

Other (OTH)

AF:

0.0341

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

307

613

920

1226

1533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0306

Hom.:

Bravo

AF:

0.0558

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Smith-Lemli-Opitz syndrome

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Feb 28, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.010

(source)

DANN

Benign

0.86

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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