chr11-71439474-T-G

Position:

• chr11-71439474-T-G

Variant summary

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

The NM_001360.3(DHCR7):​c.627-391A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,132 control chromosomes in the GnomAD database, including 8,044 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 0.31 (8044 hom., cov: 33)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.627-391A>C		intron_variant		ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2	c.627-391A>C		intron_variant			NP_001157289.1
DHCR7	XM_011544777.3	c.627-391A>C		intron_variant			XP_011543079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.627-391A>C		intron_variant		1	NM_001360.3	ENSP00000347717	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47132 AN: 152014 Hom.: 8041 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.310 AC: 47141 AN: 152132 Hom.: 8044 Cov.: 33 AF XY: 0.321 AC XY: 23886 AN XY: 74356

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.340

Alfa AF: 0.272 Hom.: 1192

Bravo AF: 0.300

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.060
DANN	Benign	0.72

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: rs1790324; hg19: chr11-71150520;