rs1790345

Variant names:

• chr11-71434895-G-A
• rs1790345
• NM_001360.3:c.*480C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-71434895-G-A
• chr11-71434895-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360.3(DHCR7):​c.*480C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 355,294 control chromosomes in the GnomAD database, including 16,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6733 hom., cov: 32)
  • Exomes 𝑓: 0.30 (10083 hom.)
• Consequence: DHCR7 NM_001360.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.02
• Publications: 20 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-71434895-G-A is Benign according to our data. Variant chr11-71434895-G-A is described in ClinVar as Benign. ClinVar VariationId is 305941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	NM_001360.3	MANE Select	c.*480C>T		3_prime_UTR	Exon 9 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.*480C>T		3_prime_UTR	Exon 10 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.*480C>T		3_prime_UTR	Exon 9 of 9	NP_001412037.1	A0A804HJQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000355527.8	TSL:1 MANE Select	c.*480C>T		3_prime_UTR	Exon 9 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.*480C>T		3_prime_UTR	Exon 9 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.*480C>T		3_prime_UTR	Exon 8 of 8	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43532 AN: 151796 Hom.: 6733 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.317

GnomAD4 exome AF: 0.295 AC: 60012 AN: 203378 Hom.: 10083 Cov.: 0 AF XY: 0.315 AC XY: 35281 AN XY: 112058

African (AFR) AF: 0.350 AC: 1845 AN: 5274

American (AMR) AF: 0.230 AC: 2617 AN: 11374

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 973 AN: 4492

East Asian (EAS) AF: 0.405 AC: 3349 AN: 8272

South Asian (SAS) AF: 0.468 AC: 20117 AN: 42942

European-Finnish (FIN) AF: 0.355 AC: 3125 AN: 8808

Middle Eastern (MID) AF: 0.300 AC: 204 AN: 680

European-Non Finnish (NFE) AF: 0.224 AC: 25056 AN: 111834

Other (OTH) AF: 0.281 AC: 2726 AN: 9702

GnomAD4 genome AF: 0.287 AC: 43533 AN: 151916 Hom.: 6733 Cov.: 32 AF XY: 0.299 AC XY: 22191 AN XY: 74276

African (AFR) AF: 0.345 AC: 14300 AN: 41440

American (AMR) AF: 0.279 AC: 4253 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2010 AN: 5108

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3976 AN: 10548

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14916 AN: 67950

Other (OTH) AF: 0.321 AC: 675 AN: 2104

Alfa AF: 0.246 Hom.: 9916

Bravo AF: 0.274

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Smith-Lemli-Opitz syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.028
DANN	Benign	0.69
PhyloP100		-4.0
Mutation Taster		=99/1	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: rs1790345; hg19: chr11-71145941;