dbSNP rs12419334: DHCR7:c.*397A>G (chr11-71428426-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001425120.1(DHCR7):c.*397A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 154,492 control chromosomes in the GnomAD database, including 27,453 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 27038 hom., cov: 33)

Exomes 𝑓: 0.55 ( 415 hom. )

Consequence

DHCR7
NM_001425120.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.634

Publications

8 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), G2P, Myriad Women’s Health, ClinGen, Orphanet, Laboratory for Molecular Medicine

DHCR7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425120.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	NM_001425120.1		c.*397A>G		3_prime_UTR	Exon 9 of 9	NP_001412049.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000534795.5	TSL:1	c.*397A>G		3_prime_UTR	Exon 3 of 3	ENSP00000432256.1	H0YCS7

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86555

AN:

151976

Hom.:

27032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.548

GnomAD4 exome

AF:

0.550

AC:

1317

AN:

2396

Hom.:

415

Cov.:

AF XY:

0.527

AC XY:

675

AN XY:

1280

show subpopulations

African (AFR)

AF:

0.174

AC:

AN:

American (AMR)

AF:

0.498

AC:

270

AN:

542

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

AN:

East Asian (EAS)

AF:

0.255

AC:

AN:

102

South Asian (SAS)

AF:

0.175

AC:

AN:

274

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.690

AC:

873

AN:

1266

Other (OTH)

AF:

0.565

AC:

AN:

108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.569

AC:

86588

AN:

152096

Hom.:

27038

Cov.:

AF XY:

0.554

AC XY:

41174

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.374

AC:

15499

AN:

41468

American (AMR)

AF:

0.527

AC:

8060

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

2142

AN:

3470

East Asian (EAS)

AF:

0.385

AC:

1993

AN:

5178

South Asian (SAS)

AF:

0.208

AC:

1004

AN:

4824

European-Finnish (FIN)

AF:

0.569

AC:

6018

AN:

10568

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.735

AC:

49971

AN:

67990

Other (OTH)

AF:

0.542

AC:

1144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.596

Hom.:

4862

Bravo

AF:

0.567

Asia WGS

AF:

0.281

AC:

980

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.1

(source)

DANN

Benign

0.60

PhyloP100

-0.63

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over