rs718265

chr1-54854229-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014762.4(DHCR24):c.1026T>C(p.Ile342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,612,104 control chromosomes in the GnomAD database, including 385,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33909 hom., cov: 32)
  • Exomes 𝑓: 0.69 (351153 hom.)
• Consequence: DHCR24 NM_014762.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.67

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-54854229-A-G is Benign according to our data. Variant chr1-54854229-A-G is described in ClinVar as [Benign]. Clinvar id is 297654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-54854229-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHCR24	NM_014762.4	c.1026T>C	p.Ile342=	synonymous_variant	7/9	ENST00000371269.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHCR24	ENST00000371269.9	c.1026T>C	p.Ile342=	synonymous_variant	7/9	1	NM_014762.4	P1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100905 AN: 151792 Hom.: 33896 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.653

GnomAD3 exomes AF: 0.662 AC: 164898 AN: 249076 Hom.: 56109 AF XY: 0.677 AC XY: 91260 AN XY: 134868

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.806

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.691

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.691 AC: 1008540 AN: 1460194 Hom.: 351153 Cov.: 42 AF XY: 0.695 AC XY: 504600 AN XY: 726340

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.698

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.665 AC: 100966 AN: 151910 Hom.: 33909 Cov.: 32 AF XY: 0.670 AC XY: 49757 AN XY: 74244

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.656

Alfa AF: 0.677 Hom.: 79871

Bravo AF: 0.639

Asia WGS AF: 0.603 AC: 2102 AN: 3478

EpiCase AF: 0.685

EpiControl AF: 0.685

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Desmosterolosis Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.76

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: rs718265; hg19: chr1-55319902; COSMIC: COSV64875204; COSMIC: COSV64875204;