rs3797371

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
HSD17B4NM_000414.4 linkuse as main transcriptc.1994-2354A>G intron_variant ENST00000510025.7 NP_000405.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSD17B4ENST00000510025.7 linkuse as main transcriptc.1994-2354A>G intron_variant 2 NM_000414.4 ENSP00000424940 P1P51659-1

Frequencies

GnomAD3 genomes
AF:
0.103
AC:
15670
AN:
151998
Hom.:
969
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.0524
Gnomad4 AMR
AF:
0.101
Gnomad4 ASJ
AF:
0.131
Gnomad4 EAS
AF:
0.0972
Gnomad4 SAS
AF:
0.159
Gnomad4 FIN
AF:
0.0815
Gnomad4 NFE
AF:
0.130
Gnomad4 OTH
AF:
0.113
Alfa
AF:
0.116
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3797371; hg19: chr5-118869764; API