Genetic Variant HSD17B2:c.-133T>C (chr16-82035292-T-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_002153.3(HSD17B2):c.-133T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 733,832 control chromosomes in the GnomAD database, including 145,024 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 0.65 ( 32513 hom., cov: 30)

Exomes 𝑓: 0.62 ( 112511 hom. )

Consequence

HSD17B2
NM_002153.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

15 publications found

Variant links:

Genes affected

HSD17B2 (HGNC:5211): (hydroxysteroid 17-beta dehydrogenase 2) Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in response to retinoic acid. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B2 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3 link	c.-133T>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1 link	c.-133T>C		5_prime_UTR_variant	Exon 1 of 4		XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HSD17B2	ENST00000199936.9 link	c.-133T>C	5_prime_UTR_variant	Exon 1 of 5	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000566213.1 link	c.-133T>C	5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000457943.1
HSD17B2	ENST00000563491.5 link	c.-144+144T>C	intron_variant	Intron 1 of 2	3		ENSP00000455992.1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98851

AN:

151852

Hom.:

32464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.614

GnomAD4 exome

AF:

0.617

AC:

358893

AN:

581862

Hom.:

112511

Cov.:

AF XY:

0.612

AC XY:

184959

AN XY:

301998

show subpopulations

African (AFR)

AF:

0.685

AC:

10573

AN:

15424

American (AMR)

AF:

0.682

AC:

14476

AN:

21226

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

7594

AN:

14692

East Asian (EAS)

AF:

0.364

AC:

12140

AN:

33334

South Asian (SAS)

AF:

0.558

AC:

27937

AN:

50040

European-Finnish (FIN)

AF:

0.725

AC:

24250

AN:

33470

Middle Eastern (MID)

AF:

0.481

AC:

1063

AN:

2212

European-Non Finnish (NFE)

AF:

0.636

AC:

242186

AN:

380910

Other (OTH)

AF:

0.611

AC:

18674

AN:

30554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7122

14245

21367

28490

35612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3214

6428

9642

12856

16070

<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:

0.651

AC:

98955

AN:

151970

Hom.:

32513

Cov.:

AF XY:

0.654

AC XY:

48589

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.694

AC:

28752

AN:

41456

American (AMR)

AF:

0.683

AC:

10430

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1796

AN:

3470

East Asian (EAS)

AF:

0.422

AC:

2179

AN:

5168

South Asian (SAS)

AF:

0.567

AC:

2714

AN:

4788

European-Finnish (FIN)

AF:

0.736

AC:

7767

AN:

10558

Middle Eastern (MID)

AF:

0.417

AC:

121

AN:

290

European-Non Finnish (NFE)

AF:

0.635

AC:

43168

AN:

67956

Other (OTH)

AF:

0.614

AC:

1296

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1738

3476

5213

6951

8689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.633

Hom.:

50773

Bravo

AF:

0.648

Asia WGS

AF:

0.541

AC:

1882

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.8

(source)

DANN

Benign

0.65

PhyloP100

-0.089

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=300/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over