rs12419334

chr11-71428426-T-C

Variant summary

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

The ENST00000534795.5(DHCR7):c.*397A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 154,492 control chromosomes in the GnomAD database, including 27,453 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 0.57 (27038 hom., cov: 33)
  • Exomes 𝑓: 0.55 (415 hom.)
• Consequence: DHCR7 ENST00000534795.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR7	ENST00000534795.5	c.*397A>G		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86555 AN: 151976 Hom.: 27032 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.550 AC: 1317 AN: 2396 Hom.: 415 Cov.: 0 AF XY: 0.527 AC XY: 675 AN XY: 1280

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.569 AC: 86588 AN: 152096 Hom.: 27038 Cov.: 33 AF XY: 0.554 AC XY: 41174 AN XY: 74352

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.542

Alfa AF: 0.603 Hom.: 4811

Bravo AF: 0.567

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.1
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12419334; hg19: chr11-71139472;