rs257977

Variant names:

• chr5-119466526-T-G
• rs257977
• NM_000414.4:c.113-7382T>G

Variant summary

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

The NM_000414.4(HSD17B4):​c.113-7382T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,252 control chromosomes in the GnomAD database, including 314 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 0.064 (314 hom., cov: 33)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B4	NM_000414.4	c.113-7382T>G		intron_variant	Intron 2 of 23	ENST00000510025.7	NP_000405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7	c.113-7382T>G		intron_variant	Intron 2 of 23	2	NM_000414.4	ENSP00000424940.3

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9735 AN: 152134 Hom.: 313 Cov.: 33

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0640 AC: 9738 AN: 152252 Hom.: 314 Cov.: 33 AF XY: 0.0634 AC XY: 4719 AN XY: 74454

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.0624

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0634 Hom.: 469

Bravo AF: 0.0643

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs257977; hg19: chr5-118802221;