NM_000414.4:c.2122-1626C>T

Variant names:

• chr5-119540279-C-T
• rs3850201
• NM_000414.4:c.2122-1626C>T

Variant summary

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

The NM_000414.4(HSD17B4):​c.2122-1626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,116 control chromosomes in the GnomAD database, including 2,161 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 0.13 (2161 hom., cov: 31)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B4	NM_000414.4	MANE Select	c.2122-1626C>T		intron	N/A	NP_000405.1
	HSD17B4	NM_001199291.3		c.2197-1626C>T		intron	N/A	NP_001186220.1
	HSD17B4	NM_001374497.1		c.2113-1626C>T		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.2122-1626C>T		intron	N/A	ENSP00000424940.3
	HSD17B4	ENST00000509514.6	TSL:1	c.2053-1626C>T		intron	N/A	ENSP00000426272.2
	HSD17B4	ENST00000414835.7	TSL:2	c.2197-1626C>T		intron	N/A	ENSP00000411960.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20380 AN: 151998 Hom.: 2163 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.134 AC: 20396 AN: 152116 Hom.: 2161 Cov.: 31 AF XY: 0.131 AC XY: 9718 AN XY: 74378

African (AFR) AF: 0.294 AC: 12193 AN: 41458

American (AMR) AF: 0.0889 AC: 1359 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 300 AN: 3462

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4818

European-Finnish (FIN) AF: 0.0848 AC: 898 AN: 10590

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0763 AC: 5187 AN: 68004

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.121 Hom.: 204

Bravo AF: 0.144

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.081
DANN	Benign	0.49
PhyloP100		-1.4
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: rs3850201; hg19: chr5-118875974;