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GeneBe

rs718265

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.67
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]

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ACMG classification

Classification made for transcript

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
DHCR24NM_014762.4 linkuse as main transcriptc.1026T>C p.Ile342= synonymous_variant 7/9 ENST00000371269.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DHCR24ENST00000371269.9 linkuse as main transcriptc.1026T>C p.Ile342= synonymous_variant 7/91 NM_014762.4 P1Q15392-1

Frequencies

GnomAD3 genomes
AF:
0.665
AC:
100905
AN:
151792
Hom.:
33896
Cov.:
32
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
GnomAD3 exomes
AF:
0.662
AC:
164898
AN:
249076
Hom.:
56109
AF XY:
0.677
AC XY:
91260
AN XY:
134868
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 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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Desmosterolosis Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingGenome-Nilou LabJul 30, 2021- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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