11-71448718-T-G

Position:

• chr11-71448718-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000529369.2(DHCR7-DT):​n.157T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,220 control chromosomes in the GnomAD database, including 25,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (25663 hom., cov: 34)
  • Exomes 𝑓: 0.65 (8 hom.)
• Consequence: DHCR7-DT ENST00000529369.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0990

Genes affected

DHCR7-DT (HGNC:56822): (DHCR7 divergent transcript)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-71448718-T-G is Benign according to our data. Variant chr11-71448718-T-G is described in ClinVar as [Benign]. Clinvar id is 1263320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7-DT	ENST00000529369.2	n.157T>G		non_coding_transcript_exon_variant	1/2	2
DHCR7	ENST00000527452.1	c.-131-984A>C		intron_variant		4		ENSP00000436007

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81397 AN: 152068 Hom.: 25661 Cov.: 34

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.647 AC: 22 AN: 34 Hom.: 8 Cov.: 0 AF XY: 0.654 AC XY: 17 AN XY: 26

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.692

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.535 AC: 81413 AN: 152186 Hom.: 25663 Cov.: 34 AF XY: 0.520 AC XY: 38705 AN XY: 74394

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.516

Alfa AF: 0.623 Hom.: 3985

Bravo AF: 0.527

Asia WGS AF: 0.254 AC: 888 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.4
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28364617; hg19: chr11-71159764;