Variant chr11-71435202-AAGCAAGGAACAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001360.3(DHCR7):c.*161_*172del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 753,938 control chromosomes in the GnomAD database, including 32,025 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6455 hom., cov: 20)

Exomes 𝑓: 0.28 ( 25570 hom. )

Consequence

DHCR7
NM_001360.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.00

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-71435202-AAGCAAGGAACAG-A is Benign according to our data. Variant chr11-71435202-AAGCAAGGAACAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 305948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-71435202-AAGCAAGGAACAG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
DHCR7	NM_001360.3 linkuse as main transcript	c.161_172del	3_prime_UTR_variant	9/9	ENST00000355527.8
DHCR7	NM_001163817.2 linkuse as main transcript	c.161_172del	3_prime_UTR_variant	9/9
DHCR7	XM_011544777.3 linkuse as main transcript	c.352_363del	3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR7	ENST00000355527.8 linkuse as main transcript	c.161_172del		3_prime_UTR_variant	9/9	1	NM_001360.3	P1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42754

AN:

151904

Hom.:

6454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.291

AC:

40878

AN:

140566

Hom.:

6476

AF XY:

0.303

AC XY:

23353

AN XY:

77022

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.277

AC:

166954

AN:

601914

Hom.:

25570

AF XY:

0.286

AC XY:

92577

AN XY:

323822

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.463

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.281

AC:

42756

AN:

152024

Hom.:

6455

Cov.:

AF XY:

0.293

AC XY:

21779

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.244

Hom.:

843

Bravo

AF:

0.268

Asia WGS

AF:

0.368

AC:

1278

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Smith-Lemli-Opitz syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 09, 2018	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over