rs1630498

Positions:

• chr11-71439739-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360.3(DHCR7):​c.627-656T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,072 control chromosomes in the GnomAD database, including 6,563 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 0.28 (6563 hom., cov: 32)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.627-656T>G		intron_variant		ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2	c.627-656T>G		intron_variant			NP_001157289.1
DHCR7	XM_011544777.3	c.627-656T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.627-656T>G		intron_variant		1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320.1	c.42-656T>G		intron_variant				ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43075 AN: 151954 Hom.: 6564 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.283 AC: 43074 AN: 152072 Hom.: 6563 Cov.: 32 AF XY: 0.296 AC XY: 21973 AN XY: 74336

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.319

Alfa AF: 0.253 Hom.: 2426

Bravo AF: 0.270

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.2
DANN	Benign	0.87

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: rs1630498; hg19: chr11-71150785;