rs7122671

Variant names:

• chr11-71433422-G-A
• rs7122671
• ENST00000534795.5:c.318+4390C>T

Variant summary

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

The ENST00000534795.5(DHCR7):​c.318+4390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,234 control chromosomes in the GnomAD database, including 646 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 0.087 (646 hom., cov: 33)
• Consequence: DHCR7 ENST00000534795.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHCR7	NM_001425120.1	c.963+4390C>T		intron_variant	Intron 8 of 8		NP_001412049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR7	ENST00000534795.5	c.318+4390C>T		intron_variant	Intron 2 of 2	1		ENSP00000432256.1

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13226 AN: 152116 Hom.: 644 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.0869 AC: 13228 AN: 152234 Hom.: 646 Cov.: 33 AF XY: 0.0892 AC XY: 6640 AN XY: 74458

African (AFR) AF: 0.131 AC: 5454 AN: 41518

American (AMR) AF: 0.0668 AC: 1022 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 308 AN: 3472

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5182

South Asian (SAS) AF: 0.126 AC: 610 AN: 4828

European-Finnish (FIN) AF: 0.0859 AC: 911 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0615 AC: 4181 AN: 68022

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.0764 Hom.: 48

Bravo AF: 0.0840

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.41
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs7122671; hg19: chr11-71144468;