rs11606033

Variant names:

• chr11-71443158-A-G
• rs11606033
• NM_001360.3:c.322-805T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360.3(DHCR7):​c.322-805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,110 control chromosomes in the GnomAD database, including 27,498 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 0.58 (27498 hom., cov: 33)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 10 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• 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 rank	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.322-805T>C		intron_variant	Intron 4 of 8	ENST00000355527.8	NP_001351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.322-805T>C		intron_variant	Intron 4 of 8	1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320.1	c.-264-805T>C		intron_variant	Intron 3 of 7			ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87836 AN: 151990 Hom.: 27468 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87911 AN: 152110 Hom.: 27498 Cov.: 33 AF XY: 0.562 AC XY: 41790 AN XY: 74356

African (AFR) AF: 0.404 AC: 16754 AN: 41474

American (AMR) AF: 0.537 AC: 8201 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1892 AN: 5180

South Asian (SAS) AF: 0.204 AC: 986 AN: 4826

European-Finnish (FIN) AF: 0.569 AC: 6011 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50016 AN: 67984

Other (OTH) AF: 0.547 AC: 1156 AN: 2114

Alfa AF: 0.636 Hom.: 4147

Bravo AF: 0.578

Asia WGS AF: 0.265 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.35
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11606033; hg19: chr11-71154204;