1-54850649-A-G

Position:

• chr1-54850649-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014762.4(DHCR24):​c.*1584T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,080 control chromosomes in the GnomAD database, including 13,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (13193 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: DHCR24 NM_014762.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.746

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-54850649-A-G is Benign according to our data. Variant chr1-54850649-A-G is described in ClinVar as [Benign]. Clinvar id is 297625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHCR24	NM_014762.4	c.*1584T>C		3_prime_UTR_variant	9/9	ENST00000371269.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR24	ENST00000371269.9	c.*1584T>C		3_prime_UTR_variant	9/9	1	NM_014762.4	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59775 AN: 151954 Hom.: 13166 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.394 AC: 59868 AN: 152074 Hom.: 13193 Cov.: 32 AF XY: 0.387 AC XY: 28744 AN XY: 74342

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.382

Alfa AF: 0.329 Hom.: 14240

Bravo AF: 0.427

Asia WGS AF: 0.405 AC: 1404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Desmosterolosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7374; hg19: chr1-55316322;