rs718265

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.67

Publications

34 publications found

Variant links:

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, Orphanet, Labcorp Genetics (formerly Invitae), G2P

DHCR24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId is 297654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	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 link	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.695

AC XY:

504600

AN XY:

726340

show subpopulations

African (AFR)

AF:

0.614

AC:

20560

AN:

33462

American (AMR)

AF:

0.550

AC:

24543

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.698

AC:

18213

AN:

26076

East Asian (EAS)

AF:

0.446

AC:

17682

AN:

39682

South Asian (SAS)

AF:

0.800

AC:

68905

AN:

86106

European-Finnish (FIN)

AF:

0.744

AC:

39638

AN:

53282

Middle Eastern (MID)

AF:

0.624

AC:

3596

AN:

5764

European-Non Finnish (NFE)

AF:

0.697

AC:

774699

AN:

1110862

Other (OTH)

AF:

0.675

AC:

40704

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14560

29121

43681

58242

72802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19588

39176

58764

78352

97940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.665

AC:

100966

AN:

151910

Hom.:

33909

Cov.:

AF XY:

0.670

AC XY:

49757

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.617

AC:

25528

AN:

41366

American (AMR)

AF:

0.620

AC:

9467

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2404

AN:

3468

East Asian (EAS)

AF:

0.411

AC:

2113

AN:

5138

South Asian (SAS)

AF:

0.803

AC:

3876

AN:

4824

European-Finnish (FIN)

AF:

0.756

AC:

7995

AN:

10572

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.697

AC:

47363

AN:

67962

Other (OTH)

AF:

0.656

AC:

1382

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1759

3518

5277

7036

8795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

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

(source)

DANN

Benign

0.76

PhyloP100

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over