11-71435202-AAGCAAGGAACAG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001360.3(DHCR7):c.*161_*172del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 753,938 control chromosomes in the GnomAD database, including 32,025 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6455 hom., cov: 20)
  • Exomes 𝑓: 0.28 (25570 hom.)
• Consequence: DHCR7 NM_001360.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.00

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 -16 ACMG points.

• BP6: Variant 11-71435202-AAGCAAGGAACAG-A is Benign according to our data. Variant chr11-71435202-AAGCAAGGAACAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 305948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-71435202-AAGCAAGGAACAG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHCR7	NM_001360.3	c.*161_*172del		3_prime_UTR_variant	9/9	ENST00000355527.8
DHCR7	NM_001163817.2	c.*161_*172del		3_prime_UTR_variant	9/9
DHCR7	XM_011544777.3	c.*352_*363del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR7	ENST00000355527.8	c.*161_*172del		3_prime_UTR_variant	9/9	1	NM_001360.3	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42754 AN: 151904 Hom.: 6454 Cov.: 20

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.308

GnomAD3 exomes AF: 0.291 AC: 40878 AN: 140566 Hom.: 6476 AF XY: 0.303 AC XY: 23353 AN XY: 77022

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.462

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.277 AC: 166954 AN: 601914 Hom.: 25570 AF XY: 0.286 AC XY: 92577 AN XY: 323822

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.281 AC: 42756 AN: 152024 Hom.: 6455 Cov.: 20 AF XY: 0.293 AC XY: 21779 AN XY: 74298

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.312

Alfa AF: 0.244 Hom.: 843

Bravo AF: 0.268

Asia WGS AF: 0.368 AC: 1278 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Smith-Lemli-Opitz syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 09, 2018	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141483210; hg19: chr11-71146248;