rs718265

Variant names:

• chr1-54854229-A-G
• rs718265
• NM_014762.4:c.1026T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014762.4(DHCR24):​c.1026T>C​(p.Ile342Ile) 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:5
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DHCR24	NM_014762.4	c.1026T>C	p.Ile342Ile	synonymous_variant	Exon 7 of 9	ENST00000371269.9	NP_055577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR24	ENST00000371269.9	c.1026T>C	p.Ile342Ile	synonymous_variant	Exon 7 of 9	1	NM_014762.4	ENSP00000360316.3

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

GnomAD2 exomes AF: 0.662 AC: 164898 AN: 249076 AF XY: 0.677

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 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 AC: 20560 AN: 33462

Gnomad4 AMR exome AF: 0.550 AC: 24543 AN: 44628

Gnomad4 ASJ exome AF: 0.698 AC: 18213 AN: 26076

Gnomad4 EAS exome AF: 0.446 AC: 17682 AN: 39682

Gnomad4 SAS exome AF: 0.800 AC: 68905 AN: 86106

Gnomad4 FIN exome AF: 0.744 AC: 39638 AN: 53282

Gnomad4 NFE exome AF: 0.697 AC: 774699 AN: 1110862

Gnomad4 Remaining exome AF: 0.675 AC: 40704 AN: 60332

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 AC: 0.617125 AN: 0.617125

Gnomad4 AMR AF: 0.620 AC: 0.620055 AN: 0.620055

Gnomad4 ASJ AF: 0.693 AC: 0.693195 AN: 0.693195

Gnomad4 EAS AF: 0.411 AC: 0.41125 AN: 0.41125

Gnomad4 SAS AF: 0.803 AC: 0.803483 AN: 0.803483

Gnomad4 FIN AF: 0.756 AC: 0.756243 AN: 0.756243

Gnomad4 NFE AF: 0.697 AC: 0.696904 AN: 0.696904

Gnomad4 OTH AF: 0.656 AC: 0.655598 AN: 0.655598

Alfa AF: 0.675 Hom.: 161850

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Desmosterolosis Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.76
Mutation Taster		=92/8	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

Publications

LitVar

Other links and lift over

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