rs11603330

chr11-71442413-C-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.322-60G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,167,730 control chromosomes in the GnomAD database, including 262,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (25064 hom., cov: 32)
  • Exomes 𝑓: 0.66 (237565 hom.)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0270

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-71442413-C-A is Benign according to our data. Variant chr11-71442413-C-A is described in ClinVar as [Benign]. Clinvar id is 1177473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHCR7	NM_001360.3	c.322-60G>T		intron_variant		ENST00000355527.8
DHCR7	NM_001163817.2	c.322-60G>T		intron_variant
DHCR7	XM_011544777.3	c.322-60G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR7	ENST00000355527.8	c.322-60G>T		intron_variant		1	NM_001360.3	P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80472 AN: 151960 Hom.: 25064 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.658 AC: 668408 AN: 1015650 Hom.: 237565 AF XY: 0.643 AC XY: 336767 AN XY: 523566

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.613

GnomAD4 genome AF: 0.529 AC: 80484 AN: 152080 Hom.: 25064 Cov.: 32 AF XY: 0.515 AC XY: 38280 AN XY: 74356

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.512

Alfa AF: 0.666 Hom.: 13942

Bravo AF: 0.522

Asia WGS AF: 0.253 AC: 882 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

Genome-Nilou Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	11
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11603330; hg19: chr11-71153459; COSMIC: COSV62794714; COSMIC: COSV62794714;