rs26180

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_000414.4(HSD17B4):c.-75C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000559 in 1,610,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

HSD17B4
NM_000414.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.0680

Publications

10 publications found

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]

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)

HSD17B4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000589 (859/1458816) while in subpopulation NFE AF = 0.000732 (813/1110840). AF 95% confidence interval is 0.00069. There are 0 homozygotes in GnomAdExome4. There are 413 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B4	NM_000414.4	MANE Select	c.-75C>A	5_prime_UTR	Exon 1 of 24	NP_000405.1	A0A0S2Z4J1
HSD17B4	NM_001199291.3		c.-253C>A	5_prime_UTR	Exon 1 of 25	NP_001186220.1	P51659-2
HSD17B4	NM_001374497.1		c.-75C>A	5_prime_UTR	Exon 1 of 24	NP_001361426.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B4	ENST00000510025.7	TSL:2 MANE Select	c.-75C>A	5_prime_UTR	Exon 1 of 24	ENSP00000424940.3	P51659-1
HSD17B4	ENST00000509514.6	TSL:1	c.-75C>A	5_prime_UTR	Exon 1 of 24	ENSP00000426272.2	E7EPL9
HSD17B4	ENST00000414835.7	TSL:2	c.-253C>A	5_prime_UTR	Exon 1 of 25	ENSP00000411960.3	P51659-2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000589

AC:

859

AN:

1458816

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

413

AN XY:

725834

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33422

American (AMR)

AF:

0.000314

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.000101

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4650

European-Non Finnish (NFE)

AF:

0.000732

AC:

813

AN:

1110840

Other (OTH)

AF:

0.000332

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000276

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41522

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

924

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bifunctional peroxisomal enzyme deficiency (1)

Perrault syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.1

(source)

DANN

Benign

0.62

PhyloP100

0.068

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over