11-71434895-G-A

Position:

• chr11-71434895-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360.3(DHCR7):​c.*480C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 355,294 control chromosomes in the GnomAD database, including 16,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6733 hom., cov: 32)
  • Exomes 𝑓: 0.30 (10083 hom.)
• Consequence: DHCR7 NM_001360.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.02

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-71434895-G-A is Benign according to our data. Variant chr11-71434895-G-A is described in ClinVar as [Benign]. Clinvar id is 305941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.*480C>T		3_prime_UTR_variant	9/9	ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2	c.*480C>T		3_prime_UTR_variant	9/9		NP_001157289.1
DHCR7	XM_011544777.3	c.*671C>T		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527	c.*480C>T		3_prime_UTR_variant	9/9	1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320	c.*480C>T		3_prime_UTR_variant	8/8			ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43532 AN: 151796 Hom.: 6733 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.317

GnomAD4 exome AF: 0.295 AC: 60012 AN: 203378 Hom.: 10083 Cov.: 0 AF XY: 0.315 AC XY: 35281 AN XY: 112058

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.287 AC: 43533 AN: 151916 Hom.: 6733 Cov.: 32 AF XY: 0.299 AC XY: 22191 AN XY: 74276

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.321

Alfa AF: 0.231 Hom.: 4727

Bravo AF: 0.274

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Smith-Lemli-Opitz syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.028
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs1790345; hg19: chr11-71145941;