chr1-54876242-T-G

Variant names:

• chr1-54876242-T-G
• rs638944
• NM_014762.4:c.388-195A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014762.4(DHCR24):​c.388-195A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,966 control chromosomes in the GnomAD database, including 21,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.51 (21052 hom., cov: 33)
• Consequence: DHCR24 NM_014762.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.266
• Publications: 12 publications found

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

ENSG00000287724 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-54876242-T-G is Benign according to our data. Variant chr1-54876242-T-G is described in ClinVar as Benign. ClinVar VariationId is 1260254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014762.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR24	NM_014762.4	MANE Select	c.388-195A>C		intron	N/A	NP_055577.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR24	ENST00000371269.9	TSL:1 MANE Select	c.388-195A>C		intron	N/A	ENSP00000360316.3
	DHCR24	ENST00000535035.6	TSL:1	c.388-195A>C		intron	N/A	ENSP00000440191.3
	DHCR24	ENST00000436604.2	TSL:3	c.388-195A>C		intron	N/A	ENSP00000416585.2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77609 AN: 151848 Hom.: 21053 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.511 AC: 77625 AN: 151966 Hom.: 21052 Cov.: 33 AF XY: 0.520 AC XY: 38629 AN XY: 74286

African (AFR) AF: 0.355 AC: 14686 AN: 41402

American (AMR) AF: 0.448 AC: 6845 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5170

South Asian (SAS) AF: 0.698 AC: 3362 AN: 4816

European-Finnish (FIN) AF: 0.716 AC: 7558 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39576 AN: 67964

Other (OTH) AF: 0.505 AC: 1067 AN: 2112

Alfa AF: 0.549 Hom.: 88790

Bravo AF: 0.474

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.27
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs638944; hg19: chr1-55341915;