rs2002064

Variant names:

• chr11-71452374-A-G
• rs2002064
• ENST00000527452.1:c.-132+320T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-71452374-A-G
• chr11-71452374-A-T

Variant summary

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

The ENST00000527452.1(DHCR7):​c.-132+320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,046 control chromosomes in the GnomAD database, including 6,402 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 (6402 hom., cov: 32)
• Consequence: DHCR7 ENST00000527452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7-DT	NR_186309.1		n.*217A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000527452.1	TSL:4	c.-132+320T>C		intron	N/A	ENSP00000436007.1	E9PRL8
	DHCR7-DT	ENST00000529369.3	TSL:2	n.*209A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42413 AN: 151928 Hom.: 6403 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.279 AC: 42408 AN: 152046 Hom.: 6402 Cov.: 32 AF XY: 0.292 AC XY: 21678 AN XY: 74316

African (AFR) AF: 0.329 AC: 13640 AN: 41462

American (AMR) AF: 0.299 AC: 4574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2057 AN: 5172

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3828 AN: 10550

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14298 AN: 67980

Other (OTH) AF: 0.316 AC: 666 AN: 2106

Alfa AF: 0.245 Hom.: 774

Bravo AF: 0.268

Asia WGS AF: 0.373 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.19
PhyloP100		-0.23
PromoterAI		-0.056	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2002064;

hg19: chr11-71163420;