Menu
GeneBe

chr5-119452501-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000414.4(HSD17B4):​c.-75C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,610,302 control chromosomes in the GnomAD database, including 183,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15155 hom., cov: 33)
Exomes 𝑓: 0.48 ( 168189 hom. )

Consequence

HSD17B4
NM_000414.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0680
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 5-119452501-C-G is Benign according to our data. Variant chr5-119452501-C-G is described in ClinVar as [Benign]. Clinvar id is 350457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSD17B4NM_000414.4 linkuse as main transcriptc.-75C>G 5_prime_UTR_variant 1/24 ENST00000510025.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSD17B4ENST00000510025.7 linkuse as main transcriptc.-75C>G 5_prime_UTR_variant 1/242 NM_000414.4 P1P51659-1

Frequencies

GnomAD3 genomes
AF:
0.433
AC:
65737
AN:
151990
Hom.:
15142
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.273
Gnomad AMI
AF:
0.675
Gnomad AMR
AF:
0.494
Gnomad ASJ
AF:
0.548
Gnomad EAS
AF:
0.499
Gnomad SAS
AF:
0.383
Gnomad FIN
AF:
0.548
Gnomad MID
AF:
0.449
Gnomad NFE
AF:
0.487
Gnomad OTH
AF:
0.464
GnomAD4 exome
AF:
0.477
AC:
695856
AN:
1458194
Hom.:
168189
Cov.:
33
AF XY:
0.475
AC XY:
344384
AN XY:
725544
show subpopulations
Gnomad4 AFR exome
AF:
0.266
Gnomad4 AMR exome
AF:
0.571
Gnomad4 ASJ exome
AF:
0.557
Gnomad4 EAS exome
AF:
0.463
Gnomad4 SAS exome
AF:
0.374
Gnomad4 FIN exome
AF:
0.557
Gnomad4 NFE exome
AF:
0.483
Gnomad4 OTH exome
AF:
0.464
GnomAD4 genome
AF:
0.432
AC:
65786
AN:
152108
Hom.:
15155
Cov.:
33
AF XY:
0.434
AC XY:
32290
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.273
Gnomad4 AMR
AF:
0.495
Gnomad4 ASJ
AF:
0.548
Gnomad4 EAS
AF:
0.499
Gnomad4 SAS
AF:
0.383
Gnomad4 FIN
AF:
0.548
Gnomad4 NFE
AF:
0.487
Gnomad4 OTH
AF:
0.461
Alfa
AF:
0.331
Hom.:
924
Bravo
AF:
0.428
Asia WGS
AF:
0.456
AC:
1580
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Bifunctional peroxisomal enzyme deficiency Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Perrault syndrome 1 Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.7
DANN
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs26180; hg19: chr5-118788196; COSMIC: COSV56333370; COSMIC: COSV56333370; API