1-54867852-C-T

Variant names:

• chr1-54867852-C-T
• rs600491
• NM_014762.4:c.877-2406G>A

Variant summary

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

The NM_014762.4(DHCR24):​c.877-2406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,064 control chromosomes in the GnomAD database, including 18,997 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 0.48 (18997 hom., cov: 32)
• Consequence: DHCR24 NM_014762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 8 publications found

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]

DHCR24 Gene-Disease associations (from GenCC):

• desmosterolosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014762.4. 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
	DHCR24	NM_014762.4	MANE Select	c.877-2406G>A		intron	N/A	NP_055577.1	Q15392-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR24	ENST00000371269.9	TSL:1 MANE Select	c.877-2406G>A		intron	N/A	ENSP00000360316.3	Q15392-1
	DHCR24	ENST00000535035.6	TSL:1	c.877-2406G>A		intron	N/A	ENSP00000440191.3	A0A0A0MTI1
	DHCR24	ENST00000907938.1		c.913-2406G>A		intron	N/A	ENSP00000577997.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72408 AN: 151946 Hom.: 19003 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.476 AC: 72408 AN: 152064 Hom.: 18997 Cov.: 32 AF XY: 0.483 AC XY: 35878 AN XY: 74348

African (AFR) AF: 0.295 AC: 12233 AN: 41476

American (AMR) AF: 0.430 AC: 6575 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1868 AN: 3466

East Asian (EAS) AF: 0.155 AC: 799 AN: 5152

South Asian (SAS) AF: 0.653 AC: 3147 AN: 4820

European-Finnish (FIN) AF: 0.669 AC: 7070 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39133 AN: 67980

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.521 Hom.: 21357

Bravo AF: 0.439

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		-0.70
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: rs600491; hg19: chr1-55333525;