dbSNP rs8191246: HSD17B2:p.Ter388Trpext*? (chr16-82098435-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4BA1

The NM_002153.3(HSD17B2):c.1163A>G(p.Ter388Trpext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,589,486 control chromosomes in the GnomAD database, including 270 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 0.019 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 200 hom. )

Consequence

HSD17B2
NM_002153.3 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

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:

HSD17B2-AS1 (HGNC:56281): (HSD17B2 antisense RNA 1)

HSD17B2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM4

Stoplost variant in NM_002153.3 Downstream stopcodon found after 444 codons.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3 link	c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 5 of 5	ENST00000199936.9	NP_002144.1	P37059

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD17B2	ENST00000199936.9 link	c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 5 of 5	1	NM_002153.3	ENSP00000199936.4	P37059
HSD17B2	ENST00000566838.2 link	c.*7259A>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000456471.1	H3BRZ6
HSD17B2-AS1	ENST00000567021.2 link	n.44-27246T>C		intron_variant	Intron 1 of 3	5
HSD17B2	ENST00000568090.5 link	c.*94A>G		downstream_gene_variant		3		ENSP00000456529.1	H3BS44

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2930

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0504

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0127

AC:

2939

AN:

230874

AF XY:

0.0125

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0468

Gnomad FIN exome

AF:

0.000245

Gnomad NFE exome

AF:

0.000787

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00570

AC:

8191

AN:

1437162

Hom.:

200

Cov.:

AF XY:

0.00637

AC XY:

4541

AN XY:

712546

show subpopulations

African (AFR)

AF:

0.0581

AC:

1876

AN:

32282

American (AMR)

AF:

0.00333

AC:

135

AN:

40594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24820

East Asian (EAS)

AF:

0.0415

AC:

1638

AN:

39428

South Asian (SAS)

AF:

0.0375

AC:

3089

AN:

82308

European-Finnish (FIN)

AF:

0.000171

AC:

AN:

52504

Middle Eastern (MID)

AF:

0.00569

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.000680

AC:

748

AN:

1100398

Other (OTH)

AF:

0.0112

AC:

664

AN:

59208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

407

813

1220

1626

2033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0193

AC:

2941

AN:

152324

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0550

AC:

2285

AN:

41578

American (AMR)

AF:

0.00575

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0500

AC:

259

AN:

5184

South Asian (SAS)

AF:

0.0498

AC:

240

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68024

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

272

408

544

680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00832

Hom.:

Bravo

AF:

0.0201

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0547

AC:

241

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0133

AC:

1613

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.0

(source)

DANN

Benign

0.76

Eigen

Benign

0.13

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.022

PhyloP100

0.26

Vest4

0.061

GERP RS

0.67

Mutation Taster

=186/14

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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rs8191246

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