rs7551288

Positions:

• chr1-54873006-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014762.4(DHCR24):​c.613-1393T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,100 control chromosomes in the GnomAD database, including 18,396 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 0.46 (18396 hom., cov: 32)
• Consequence: DHCR24 NM_014762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

DHCR24 (HGNC:2859): (24-dehydrocholesterol reductase) This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis. Also, reduced expression of the gene occurs in the temporal cortex of Alzheimer disease patients and overexpression has been observed in adrenal gland cancer cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHCR24	NM_014762.4	c.613-1393T>C		intron_variant		ENST00000371269.9	NP_055577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHCR24	ENST00000371269.9	c.613-1393T>C		intron_variant		1	NM_014762.4	ENSP00000360316	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70009 AN: 151982 Hom.: 18405 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.460 AC: 70004 AN: 152100 Hom.: 18396 Cov.: 32 AF XY: 0.467 AC XY: 34750 AN XY: 74370

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.461

Alfa AF: 0.543 Hom.: 48023

Bravo AF: 0.421

Asia WGS AF: 0.377 AC: 1315 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	2.8
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7551288; hg19: chr1-55338679;