Variant chr5-119477621-A-G 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_000414.4(HSD17B4):c.434+120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 772,406 control chromosomes in the GnomAD database, including 112,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20970 hom., cov: 31)

Exomes 𝑓: 0.53 ( 91063 hom. )

Consequence

HSD17B4
NM_000414.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00700

Variant links:

Genes affected

HSD17B4 (HGNC:5213): (hydroxysteroid 17-beta dehydrogenase 4) The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

HSD17B4 links:

HSD17B4 (HGNC:):

HSD17B4 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=-0.96).

BP6

Variant 5-119477621-A-G is Benign according to our data. Variant chr5-119477621-A-G is described in ClinVar as [Benign]. Clinvar id is 1185270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B4	NM_000414.4 linkuse as main transcript	c.434+120A>G		intron_variant		ENST00000510025.7	NP_000405.1	P51659-1A0A0S2Z4J1B2R659

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7 linkuse as main transcript	c.434+120A>G		intron_variant		2	NM_000414.4	ENSP00000424940.3		P51659-1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78726

AN:

151804

Hom.:

20940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.922

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.539

GnomAD4 exome

AF:

0.531

AC:

329492

AN:

620484

Hom.:

91063

Cov.:

AF XY:

0.528

AC XY:

177063

AN XY:

335638

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.935

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.557

Gnomad4 NFE exome

AF:

0.488

Gnomad4 OTH exome

AF:

0.527

GnomAD4 genome

AF:

0.519

AC:

78807

AN:

151922

Hom.:

20970

Cov.:

AF XY:

0.525

AC XY:

38946

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.494

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.922

Gnomad4 SAS

AF:

0.530

Gnomad4 FIN

AF:

0.549

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.504

Hom.:

2427

Bravo

AF:

0.520

Asia WGS

AF:

0.681

AC:

2362

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bifunctional peroxisomal enzyme deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Perrault syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.1

DANN

Benign

0.71

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