5-119460446-A-G

Position:

• chr5-119460446-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.112+4078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,276 control chromosomes in the GnomAD database, including 1,145 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 0.11 (1145 hom., cov: 32)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B4	NM_000414.4	c.112+4078A>G		intron_variant		ENST00000510025.7	NP_000405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7	c.112+4078A>G		intron_variant		2	NM_000414.4	ENSP00000424940.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16209 AN: 152158 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.106 AC: 16212 AN: 152276 Hom.: 1145 Cov.: 32 AF XY: 0.104 AC XY: 7780 AN XY: 74466

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0724 Hom.: 189

Bravo AF: 0.113

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.030
DANN	Benign	0.43

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: rs11748477; hg19: chr5-118796141;