11-71442413-C-A

Variant names:

• chr11-71442413-C-A
• rs11603330
• NM_001360.3:c.322-60G>T

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.322-60G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,167,730 control chromosomes in the GnomAD database, including 262,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (25064 hom., cov: 32)
  • Exomes 𝑓: 0.66 (237565 hom.)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0270
• Publications: 23 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: Orphanet, G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-71442413-C-A is Benign according to our data. Variant chr11-71442413-C-A is described in ClinVar as Benign. ClinVar VariationId is 1177473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	NM_001360.3	MANE Select	c.322-60G>T		intron	N/A	NP_001351.2
	DHCR7	NM_001425107.1		c.322-60G>T		intron	N/A	NP_001412036.1
	DHCR7	NM_001425108.1		c.358-60G>T		intron	N/A	NP_001412037.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000355527.8	TSL:1 MANE Select	c.322-60G>T		intron	N/A	ENSP00000347717.4
	DHCR7	ENST00000407721.6	TSL:1	c.322-60G>T		intron	N/A	ENSP00000384739.2
	DHCR7	ENST00000685320.1		c.-264-60G>T		intron	N/A	ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80472 AN: 151960 Hom.: 25064 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.658 AC: 668408 AN: 1015650 Hom.: 237565 AF XY: 0.643 AC XY: 336767 AN XY: 523566

African (AFR) AF: 0.217 AC: 5415 AN: 24998

American (AMR) AF: 0.531 AC: 21347 AN: 40228

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 14429 AN: 23012

East Asian (EAS) AF: 0.332 AC: 12371 AN: 37264

South Asian (SAS) AF: 0.215 AC: 16136 AN: 75058

European-Finnish (FIN) AF: 0.587 AC: 30641 AN: 52200

Middle Eastern (MID) AF: 0.446 AC: 2193 AN: 4920

European-Non Finnish (NFE) AF: 0.755 AC: 537746 AN: 712112

Other (OTH) AF: 0.613 AC: 28130 AN: 45858

GnomAD4 genome AF: 0.529 AC: 80484 AN: 152080 Hom.: 25064 Cov.: 32 AF XY: 0.515 AC XY: 38280 AN XY: 74356

African (AFR) AF: 0.235 AC: 9743 AN: 41474

American (AMR) AF: 0.519 AC: 7937 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5168

South Asian (SAS) AF: 0.203 AC: 980 AN: 4822

European-Finnish (FIN) AF: 0.569 AC: 6006 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49957 AN: 67968

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.655 Hom.: 16182

Bravo AF: 0.522

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Smith-Lemli-Opitz syndrome Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11603330; hg19: chr11-71153459; COSMIC: COSV62794714; COSMIC: COSV62794714;