5-119456137-G-A

Variant names:

• chr5-119456137-G-A
• rs32651
• NM_000414.4:c.59-178G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000414.4(HSD17B4):​c.59-178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,800 control chromosomes in the GnomAD database, including 20,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (20704 hom., cov: 30)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-119456137-G-A is Benign according to our data. Variant chr5-119456137-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 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.59-178G>A		intron	N/A	NP_000405.1	A0A0S2Z4J1
	HSD17B4	NM_001199291.3		c.69-178G>A		intron	N/A	NP_001186220.1	P51659-2
	HSD17B4	NM_001374497.1		c.59-178G>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.59-178G>A		intron	N/A	ENSP00000424940.3	P51659-1
	HSD17B4	ENST00000509514.6	TSL:1	c.59-178G>A		intron	N/A	ENSP00000426272.2	E7EPL9
	HSD17B4	ENST00000414835.7	TSL:2	c.69-178G>A		intron	N/A	ENSP00000411960.3	P51659-2

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78095 AN: 151684 Hom.: 20669 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.515 AC: 78183 AN: 151800 Hom.: 20704 Cov.: 30 AF XY: 0.521 AC XY: 38639 AN XY: 74198

African (AFR) AF: 0.497 AC: 20556 AN: 41338

American (AMR) AF: 0.527 AC: 8040 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3470

East Asian (EAS) AF: 0.923 AC: 4756 AN: 5154

South Asian (SAS) AF: 0.525 AC: 2526 AN: 4812

European-Finnish (FIN) AF: 0.538 AC: 5664 AN: 10524

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32839 AN: 67930

Other (OTH) AF: 0.533 AC: 1125 AN: 2112

Alfa AF: 0.499 Hom.: 2370

Bravo AF: 0.518

Asia WGS AF: 0.681 AC: 2362 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		0.59
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: rs32651; hg19: chr5-118791832;