rs3750997

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.-131-61T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,306 control chromosomes in the GnomAD database, including 27,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27938 hom., cov: 34)

Exomes 𝑓: 0.78 ( 59 hom. )

Consequence

DHCR7
NM_001360.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.938

Publications

26 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Myriad Women's Health, G2P, ClinGen, Orphanet

DHCR7 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001360.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.9).

BP6

Variant 11-71447795-A-C is Benign according to our data. Variant chr11-71447795-A-C is described in ClinVar as Benign. ClinVar VariationId is 1290900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHCR7	NM_001360.3	MANE Select	c.-131-61T>G	intron	N/A	NP_001351.2	A0A024R5F7
DHCR7	NM_001425107.1		c.-131-61T>G	intron	N/A	NP_001412036.1	A0A804HI25
DHCR7	NM_001425108.1		c.-131-61T>G	intron	N/A	NP_001412037.1	A0A804HJQ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHCR7	ENST00000355527.8	TSL:1 MANE Select	c.-131-61T>G	intron	N/A	ENSP00000347717.4	Q9UBM7
DHCR7	ENST00000407721.6	TSL:1	c.-131-61T>G	intron	N/A	ENSP00000384739.2	Q9UBM7
DHCR7	ENST00000685320.1		c.-365-61T>G	intron	N/A	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88731

AN:

151998

Hom.:

27908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.784

AC:

149

AN:

190

Hom.:

Cov.:

AF XY:

0.793

AC XY:

111

AN XY:

140

show subpopulations

African (AFR)

AF:

0.417

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.831

AC:

123

AN:

148

Other (OTH)

AF:

0.786

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.584

AC:

88806

AN:

152116

Hom.:

27938

Cov.:

AF XY:

0.569

AC XY:

42293

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.407

AC:

16899

AN:

41510

American (AMR)

AF:

0.561

AC:

8577

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2149

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2222

AN:

5168

South Asian (SAS)

AF:

0.209

AC:

1009

AN:

4826

European-Finnish (FIN)

AF:

0.568

AC:

6000

AN:

10568

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.736

AC:

50035

AN:

67980

Other (OTH)

AF:

0.552

AC:

1164

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1737

3473

5210

6946

8683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.678

Hom.:

59066

Bravo

AF:

0.585

Asia WGS

AF:

0.309

AC:

1076

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.62

(source)

DANN

Benign

0.65

PhyloP100

-0.94

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over