rs3797371

Variant names:

• chr5-119534069-A-G
• rs3797371
• NM_000414.4:c.1994-2354A>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.1994-2354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,116 control chromosomes in the GnomAD database, including 973 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 0.10 (973 hom., cov: 32)
• Consequence: HSD17B4 NM_000414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B4	NM_000414.4	c.1994-2354A>G		intron_variant	Intron 22 of 23	ENST00000510025.7	NP_000405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7	c.1994-2354A>G		intron_variant	Intron 22 of 23	2	NM_000414.4	ENSP00000424940.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15670 AN: 151998 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.103 AC: 15684 AN: 152116 Hom.: 973 Cov.: 32 AF XY: 0.102 AC XY: 7555 AN XY: 74360

African (AFR) AF: 0.0524 AC: 2175 AN: 41540

American (AMR) AF: 0.101 AC: 1543 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.0972 AC: 503 AN: 5176

South Asian (SAS) AF: 0.159 AC: 768 AN: 4824

European-Finnish (FIN) AF: 0.0815 AC: 863 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8852 AN: 67950

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.114 Hom.: 213

Bravo AF: 0.103

Asia WGS AF: 0.121 AC: 421 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		-0.88
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: rs3797371; hg19: chr5-118869764;