Genetic Variant DHCR24:c.*1824T>G (chr1-54850409-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014762.4(DHCR24):c.*1824T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 152,402 control chromosomes in the GnomAD database, including 74,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74573 hom., cov: 33)

Exomes 𝑓: 1.0 ( 33 hom. )

Consequence

DHCR24
NM_014762.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.293

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-54850409-A-C is Benign according to our data. Variant chr1-54850409-A-C is described in ClinVar as [Benign]. Clinvar id is 297623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHCR24	NM_014762.4 link	c.*1824T>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000371269.9	NP_055577.1	Q15392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR24	ENST00000371269 link	c.*1824T>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_014762.4	ENSP00000360316.3		Q15392-1

Frequencies

GnomAD3 genomes

AF:

0.989

AC:

150614

AN:

152218

Hom.:

74529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.969

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.997

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.970

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.993

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.989

AC:

150716

AN:

152336

Hom.:

74573

Cov.:

AF XY:

0.989

AC XY:

73693

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.968

Gnomad4 AMR

AF:

0.997

Gnomad4 ASJ

AF:

0.989

Gnomad4 EAS

AF:

0.992

Gnomad4 SAS

AF:

0.970

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.992

Alfa

AF:

0.990

Hom.:

4764

Bravo

AF:

0.989

Asia WGS

AF:

0.960

AC:

3337

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Desmosterolosis

Benign:1

Jan 12, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over