11-71439474-T-G

Variant names:

• chr11-71439474-T-G
• rs1790324
• NM_001360.3:c.627-391A>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.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
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360.3. 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	NM_001360.3	MANE Select	c.627-391A>C		intron	N/A	NP_001351.2
	DHCR7	NM_001425107.1		c.678-391A>C		intron	N/A	NP_001412036.1
	DHCR7	NM_001425108.1		c.663-391A>C		intron	N/A	NP_001412037.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000355527.8	TSL:1 MANE Select	c.627-391A>C		intron	N/A	ENSP00000347717.4
	DHCR7	ENST00000407721.6	TSL:1	c.627-391A>C		intron	N/A	ENSP00000384739.2
	DHCR7	ENST00000685320.1		c.42-391A>C		intron	N/A	ENSP00000509319.1

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

African (AFR) AF: 0.420 AC: 17452 AN: 41514

American (AMR) AF: 0.289 AC: 4425 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5176

South Asian (SAS) AF: 0.472 AC: 2276 AN: 4822

European-Finnish (FIN) AF: 0.376 AC: 3979 AN: 10570

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14995 AN: 67970

Other (OTH) AF: 0.340 AC: 716 AN: 2108

Alfa AF: 0.275 Hom.: 1252

Bravo AF: 0.300

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.060
DANN	Benign	0.72
PhyloP100		-1.6
PromoterAI		-0.030	Neutral
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: rs1790324; hg19: chr11-71150520;