NM_001360.3:c.963+975T>C

Variant names:

• chr11-71436837-A-G
• rs1790329
• NM_001360.3:c.963+975T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360.3(DHCR7):​c.963+975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,248 control chromosomes in the GnomAD database, including 56,428 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (56428 hom., cov: 33)
• Consequence: DHCR7 NM_001360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHCR7	NM_001360.3	c.963+975T>C		intron_variant	Intron 8 of 8	ENST00000355527.8	NP_001351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000355527.8	c.963+975T>C		intron_variant	Intron 8 of 8	1	NM_001360.3	ENSP00000347717.4
DHCR7	ENST00000685320.1	c.378+975T>C		intron_variant	Intron 7 of 7			ENSP00000509319.1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129862 AN: 152130 Hom.: 56431 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.853 AC: 129882 AN: 152248 Hom.: 56428 Cov.: 33 AF XY: 0.849 AC XY: 63217 AN XY: 74438

African (AFR) AF: 0.707 AC: 29367 AN: 41514

American (AMR) AF: 0.806 AC: 12331 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2900 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4048 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3251 AN: 4818

European-Finnish (FIN) AF: 0.945 AC: 10043 AN: 10622

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64966 AN: 68034

Other (OTH) AF: 0.861 AC: 1822 AN: 2116

Alfa AF: 0.894 Hom.: 7652

Bravo AF: 0.838

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.32
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs1790329; hg19: chr11-71147883;