Genetic Variant HSD17B13:p.Ile167Ile (chr4-87315549-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_178135.5(HSD17B13):c.501C>T(p.Ile167Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,611,580 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 154 hom. )

Consequence

HSD17B13
NM_178135.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0810

Publications

6 publications found

Variant links:

Genes affected

HSD17B13 (HGNC:18685): (hydroxysteroid 17-beta dehydrogenase 13) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 4-87315549-G-A is Benign according to our data. Variant chr4-87315549-G-A is described in ClinVar as [Benign]. Clinvar id is 3250541.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.081 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5 link	c.501C>T	p.Ile167Ile	synonymous_variant	Exon 4 of 7	ENST00000328546.5	NP_835236.2	Q7Z5P4-1
HSD17B13	NM_001136230.3 link	c.393C>T	p.Ile131Ile	synonymous_variant	Exon 3 of 6		NP_001129702.1	Q7Z5P4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5 link	c.501C>T	p.Ile167Ile	synonymous_variant	Exon 4 of 7	1	NM_178135.5	ENSP00000333300.4		Q7Z5P4-1
HSD17B13	ENST00000302219.10 link	c.393C>T	p.Ile131Ile	synonymous_variant	Exon 3 of 6	1		ENSP00000305438.6		Q7Z5P4-2

Frequencies

GnomAD3 genomes

AF:

0.00994

AC:

1513

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0105

AC:

2641

AN:

251044

AF XY:

0.0107

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00879

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0149

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0126

AC:

18348

AN:

1459320

Hom.:

154

Cov.:

AF XY:

0.0125

AC XY:

9036

AN XY:

725714

show subpopulations

African (AFR)

AF:

0.00194

AC:

AN:

33458

American (AMR)

AF:

0.00923

AC:

412

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

419

AN:

26114

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.00293

AC:

252

AN:

86096

European-Finnish (FIN)

AF:

0.0124

AC:

664

AN:

53372

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0141

AC:

15669

AN:

1109966

Other (OTH)

AF:

0.0134

AC:

807

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

775

1550

2325

3100

3875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00994

AC:

1513

AN:

152260

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

720

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41546

American (AMR)

AF:

0.0139

AC:

212

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0114

AC:

121

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

962

AN:

68010

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

150

226

301

376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00957

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HSD17B13: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.9

(source)

DANN

Benign

0.80

PhyloP100

0.081

Mutation Taster

=100/0

polymorphism

(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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4-87315549-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over