Genetic Variant NM_002153.3: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.-133T>C		5_prime_UTR	Exon 1 of 5	NP_002144.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.-133T>C	5_prime_UTR	Exon 1 of 5	ENSP00000199936.4
HSD17B2	ENST00000566213.1	TSL:3	c.-133T>C	5_prime_UTR	Exon 1 of 2	ENSP00000457943.1
HSD17B2	ENST00000563491.5	TSL:3	c.-144+144T>C	intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over