Genetic Variant NM_000414.4:c.1993+1494G>C (chr5-119532898-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000414.4(HSD17B4):c.1993+1494G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,106 control chromosomes in the GnomAD database, including 59,722 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 0.88 ( 59722 hom., cov: 32)

Consequence

HSD17B4
NM_000414.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0430

Publications

1 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: 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

HSD17B4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B4	NM_000414.4 link	c.1993+1494G>C		intron_variant	Intron 22 of 23	ENST00000510025.7	NP_000405.1	P51659-1A0A0S2Z4J1B2R659

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7 link	c.1993+1494G>C		intron_variant	Intron 22 of 23	2	NM_000414.4	ENSP00000424940.3		P51659-1

Frequencies

GnomAD3 genomes

AF:

0.884

AC:

134355

AN:

151988

Hom.:

59665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

0.892

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.892

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.855

Gnomad OTH

AF:

0.890

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

GnomAD4 genome

AF:

0.884

AC:

134466

AN:

152106

Hom.:

59722

Cov.:

AF XY:

0.878

AC XY:

65285

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.973

AC:

40441

AN:

41560

American (AMR)

AF:

0.855

AC:

13036

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

3093

AN:

3468

East Asian (EAS)

AF:

0.926

AC:

4799

AN:

5180

South Asian (SAS)

AF:

0.745

AC:

3590

AN:

4822

European-Finnish (FIN)

AF:

0.804

AC:

8485

AN:

10560

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.855

AC:

58080

AN:

67948

Other (OTH)

AF:

0.886

AC:

1872

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

775

1550

2325

3100

3875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.867

Hom.:

6685

Bravo

AF:

0.898

Asia WGS

AF:

0.814

AC:

2828

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

(source)

DANN

Benign

0.49

PhyloP100

-0.043

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over