5-119453643-A-G

Variant names:

• chr5-119453643-A-G
• rs6897978
• NM_000414.4:c.58+1010A>G

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+1010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,080 control chromosomes in the GnomAD database, including 6,921 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 0.28 (6921 hom., cov: 32)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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+1010A>G		intron	N/A	NP_000405.1	A0A0S2Z4J1
	HSD17B4	NM_001199291.3		c.68+822A>G		intron	N/A	NP_001186220.1	P51659-2
	HSD17B4	NM_001374497.1		c.58+1010A>G		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+1010A>G		intron	N/A	ENSP00000424940.3	P51659-1
	HSD17B4	ENST00000509514.6	TSL:1	c.58+1010A>G		intron	N/A	ENSP00000426272.2	E7EPL9
	HSD17B4	ENST00000414835.7	TSL:2	c.68+822A>G		intron	N/A	ENSP00000411960.3	P51659-2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42873 AN: 151962 Hom.: 6924 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.282 AC: 42895 AN: 152080 Hom.: 6921 Cov.: 32 AF XY: 0.283 AC XY: 21017 AN XY: 74364

African (AFR) AF: 0.415 AC: 17227 AN: 41472

American (AMR) AF: 0.251 AC: 3842 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 771 AN: 3464

East Asian (EAS) AF: 0.519 AC: 2677 AN: 5154

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2102 AN: 10598

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14068 AN: 67964

Other (OTH) AF: 0.242 AC: 510 AN: 2108

Alfa AF: 0.228 Hom.: 16219

Bravo AF: 0.295

Asia WGS AF: 0.350 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.64
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: rs6897978; hg19: chr5-118789338;