5-119476485-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000414.4(HSD17B4):c.349+615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 799,560 control chromosomes in the GnomAD database, including 97,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (20928 hom., cov: 31)
  • Exomes 𝑓: 0.48 (76118 hom.)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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.349+615A>G		intron_variant		ENST00000510025.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B4	ENST00000510025.7	c.349+615A>G		intron_variant		2	NM_000414.4	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78629 AN: 151856 Hom.: 20898 Cov.: 31

Gnomad AFR AF: 0.492

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: 0.478

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.481 AC: 311733 AN: 647586 Hom.: 76118 Cov.: 8 AF XY: 0.480 AC XY: 145108 AN XY: 301996

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.927

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.518 AC: 78712 AN: 151974 Hom.: 20928 Cov.: 31 AF XY: 0.524 AC XY: 38915 AN XY: 74280

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.534

Alfa AF: 0.495 Hom.: 24804

Bravo AF: 0.519

Asia WGS AF: 0.678 AC: 2351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	5.8
Dann	Benign	0.74

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: rs2678070; hg19: chr5-118812180;