11-71450017-A-G

Variant names:

• chr11-71450017-A-G
• rs7928249
• ENST00000527452.1:c.-131-2283T>C

Variant summary

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

The ENST00000527452.1(DHCR7):​c.-131-2283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,122 control chromosomes in the GnomAD database, including 28,437 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 0.59 (28437 hom., cov: 32)
• Consequence: DHCR7 ENST00000527452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 15 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-DT (HGNC:56822): (DHCR7 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527452.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7-DT	NR_186309.1		n.358+1132A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000527452.1	TSL:4	c.-131-2283T>C		intron	N/A	ENSP00000436007.1
	DHCR7-DT	ENST00000529369.3	TSL:2	n.344+1132A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89414 AN: 152004 Hom.: 28411 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.588 AC: 89489 AN: 152122 Hom.: 28437 Cov.: 32 AF XY: 0.571 AC XY: 42478 AN XY: 74364

African (AFR) AF: 0.420 AC: 17423 AN: 41506

American (AMR) AF: 0.536 AC: 8197 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2136 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1969 AN: 5170

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4826

European-Finnish (FIN) AF: 0.583 AC: 6148 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50650 AN: 67992

Other (OTH) AF: 0.558 AC: 1179 AN: 2112

Alfa AF: 0.638 Hom.: 5395

Bravo AF: 0.588

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.55
PhyloP100		-2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7928249; hg19: chr11-71161063;