rs6898518

Variant names:

• chr5-119453718-G-A
• rs6898518
• NM_000414.4:c.58+1085G>A

Variant summary

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

The NM_000414.4(HSD17B4):​c.58+1085G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,254 control chromosomes in the GnomAD database, including 1,618 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 0.14 (1618 hom., cov: 33)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 2 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: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• Perrault syndrome

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	NM_000414.4	MANE Select	c.58+1085G>A		intron	N/A	NP_000405.1	A0A0S2Z4J1
	HSD17B4	NM_001199291.3		c.68+897G>A		intron	N/A	NP_001186220.1	P51659-2
	HSD17B4	NM_001374497.1		c.58+1085G>A		intron	N/A	NP_001361426.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	ENST00000510025.7	TSL:2 MANE Select	c.58+1085G>A		intron	N/A	ENSP00000424940.3	P51659-1
	HSD17B4	ENST00000509514.6	TSL:1	c.58+1085G>A		intron	N/A	ENSP00000426272.2	E7EPL9
	HSD17B4	ENST00000414835.7	TSL:2	c.68+897G>A		intron	N/A	ENSP00000411960.3	P51659-2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21523 AN: 152136 Hom.: 1616 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.142 AC: 21553 AN: 152254 Hom.: 1618 Cov.: 33 AF XY: 0.138 AC XY: 10285 AN XY: 74448

African (AFR) AF: 0.163 AC: 6756 AN: 41540

American (AMR) AF: 0.117 AC: 1785 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3468

East Asian (EAS) AF: 0.0947 AC: 491 AN: 5184

South Asian (SAS) AF: 0.147 AC: 709 AN: 4830

European-Finnish (FIN) AF: 0.102 AC: 1078 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9655 AN: 68014

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.141 Hom.: 6007

Bravo AF: 0.144

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6898518; hg19: chr5-118789413;