rs3750997

Positions:

• chr11-71447795-A-C
• chr11-71447795-A-T

Variant summary

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

The ENST00000355527.8(DHCR7):​c.-131-61T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,306 control chromosomes in the GnomAD database, including 27,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27938 hom., cov: 34)
  • Exomes 𝑓: 0.78 (59 hom.)
• Consequence: DHCR7 ENST00000355527.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.938

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-71447795-A-C is Benign according to our data. Variant chr11-71447795-A-C is described in ClinVar as [Benign]. Clinvar id is 1290900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.-131-61T>G		intron_variant		ENST00000355527.8	NP_001351.2
DHCR7	NM_001163817.2	c.-131-61T>G		intron_variant			NP_001157289.1
DHCR7	XM_011544777.3	c.-131-61T>G		intron_variant			XP_011543079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.-131-61T>G		intron_variant		1	NM_001360.3	ENSP00000347717	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88731 AN: 151998 Hom.: 27908 Cov.: 34

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.784 AC: 149 AN: 190 Hom.: 59 Cov.: 0 AF XY: 0.793 AC XY: 111 AN XY: 140

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.786

GnomAD4 genome AF: 0.584 AC: 88806 AN: 152116 Hom.: 27938 Cov.: 34 AF XY: 0.569 AC XY: 42293 AN XY: 74352

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.552

Alfa AF: 0.687 Hom.: 47451

Bravo AF: 0.585

Asia WGS AF: 0.309 AC: 1076 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3750997; hg19: chr11-71158841;