rs32651

Positions:

• chr5-119456137-G-A
• chr5-119456137-G-C
• chr5-119456137-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000414.4(HSD17B4):​c.59-178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,800 control chromosomes in the GnomAD database, including 20,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (20704 hom., cov: 30)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-119456137-G-A is Benign according to our data. Variant chr5-119456137-G-A is described in ClinVar as [Benign]. Clinvar id is 1292701.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
HSD17B4	NM_000414.4	c.59-178G>A		intron_variant		ENST00000510025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B4	ENST00000510025.7	c.59-178G>A		intron_variant		2	NM_000414.4	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78095 AN: 151684 Hom.: 20669 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.515 AC: 78183 AN: 151800 Hom.: 20704 Cov.: 30 AF XY: 0.521 AC XY: 38639 AN XY: 74198

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.533

Alfa AF: 0.499 Hom.: 2370

Bravo AF: 0.518

Asia WGS AF: 0.681 AC: 2362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs32651; hg19: chr5-118791832;