Variant 1-119750744-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005518.4(HMGCS2):c.*5+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,134,288 control chromosomes in the GnomAD database, including 267,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34579 hom., cov: 32)

Exomes 𝑓: 0.69 ( 233054 hom. )

Consequence

HMGCS2
NM_005518.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.438

Variant links:

Genes affected

HMGCS2 (HGNC:5008): (3-hydroxy-3-methylglutaryl-CoA synthase 2) The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

HMGCS2 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=-0.92).

BP6

Variant 1-119750744-T-C is Benign according to our data. Variant chr1-119750744-T-C is described in ClinVar as [Benign]. Clinvar id is 1263157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGCS2	NM_005518.4 linkuse as main transcript	c.*5+53A>G		intron_variant		ENST00000369406.8	NP_005509.1
HMGCS2	NM_001166107.1 linkuse as main transcript	c.*5+53A>G		intron_variant			NP_001159579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGCS2	ENST00000369406.8 linkuse as main transcript	c.*5+53A>G		intron_variant		1	NM_005518.4	ENSP00000358414	P1	P54868-1
HMGCS2	ENST00000544913.2 linkuse as main transcript	c.*5+53A>G		intron_variant		2		ENSP00000439495		P54868-2

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102185

AN:

151862

Hom.:

34545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.784

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.708

GnomAD4 exome

AF:

0.687

AC:

674501

AN:

982308

Hom.:

233054

AF XY:

0.693

AC XY:

352574

AN XY:

508876

show subpopulations

Gnomad4 AFR exome

AF:

0.645

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.791

Gnomad4 EAS exome

AF:

0.620

Gnomad4 SAS exome

AF:

0.797

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.684

GnomAD4 genome

AF:

0.673

AC:

102264

AN:

151980

Hom.:

34579

Cov.:

AF XY:

0.673

AC XY:

50012

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.723

Gnomad4 ASJ

AF:

0.784

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.791

Gnomad4 FIN

AF:

0.600

Gnomad4 NFE

AF:

0.678

Gnomad4 OTH

AF:

0.702

Alfa

AF:

0.694

Hom.:

36814

Bravo

AF:

0.680

Asia WGS

AF:

0.676

AC:

2353

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.4

DANN

Benign

0.50

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