5-119522784-G-C

Variant names:

• chr5-119522784-G-C
• rs10064000
• NM_000414.4:c.1504-2432G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000510025.7(HSD17B4):​c.1504-2432G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,650 control chromosomes in the GnomAD database, including 10,762 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 0.36 (10762 hom., cov: 31)
• Consequence: HSD17B4 ENST00000510025.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• d-bifunctional protein deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Perrault syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Perrault syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510025.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	NM_000414.4	MANE Select	c.1504-2432G>C		intron	N/A	NP_000405.1
	HSD17B4	NM_001199291.3		c.1579-2432G>C		intron	N/A	NP_001186220.1
	HSD17B4	NM_001374497.1		c.1495-2432G>C		intron	N/A	NP_001361426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	ENST00000510025.7	TSL:2 MANE Select	c.1504-2432G>C		intron	N/A	ENSP00000424940.3
	HSD17B4	ENST00000509514.6	TSL:1	c.1435-2432G>C		intron	N/A	ENSP00000426272.2
	HSD17B4	ENST00000414835.7	TSL:2	c.1579-2432G>C		intron	N/A	ENSP00000411960.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54662 AN: 151532 Hom.: 10753 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.361 AC: 54701 AN: 151650 Hom.: 10762 Cov.: 31 AF XY: 0.370 AC XY: 27399 AN XY: 74070

African (AFR) AF: 0.271 AC: 11203 AN: 41308

American (AMR) AF: 0.400 AC: 6083 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3466

East Asian (EAS) AF: 0.824 AC: 4269 AN: 5180

South Asian (SAS) AF: 0.380 AC: 1821 AN: 4798

European-Finnish (FIN) AF: 0.466 AC: 4898 AN: 10512

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23652 AN: 67856

Other (OTH) AF: 0.369 AC: 777 AN: 2108

Alfa AF: 0.212 Hom.: 485

Bravo AF: 0.355

Asia WGS AF: 0.553 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.46
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10064000; hg19: chr5-118858479;