rs8191246

Variant names:

• chr16-82098435-A-G
• rs8191246
• NM_002153.3:c.1163A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-82098435-A-G
• chr16-82098435-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 15 publications found

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

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 5 of 5	NP_002144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 5 of 5	ENSP00000199936.4
	HSD17B2	ENST00000891334.1		c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 6 of 6	ENSP00000561393.1
	HSD17B2	ENST00000891335.1		c.1163A>G	p.Ter388Trpext*?	stop_lost	Exon 6 of 6	ENSP00000561394.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2930 AN: 152206 Hom.: 69 Cov.: 32

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

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.: 32 AF XY: 0.00637 AC XY: 4541 AN XY: 712546

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: 0 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: 9 AN: 52504

Middle Eastern (MID) AF: 0.00569 AC: 32 AN: 5620

European-Non Finnish (NFE) AF: 0.000680 AC: 748 AN: 1100398

Other (OTH) AF: 0.0112 AC: 664 AN: 59208

GnomAD4 genome AF: 0.0193 AC: 2941 AN: 152324 Hom.: 70 Cov.: 32 AF XY: 0.0197 AC XY: 1467 AN XY: 74494

African (AFR) AF: 0.0550 AC: 2285 AN: 41578

American (AMR) AF: 0.00575 AC: 88 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68024

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00832 Hom.: 95

Bravo AF: 0.0201

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0547 AC: 241

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0133 AC: 1613

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.0
DANN	Benign	0.76
Eigen	Benign	0.13
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.022	N
PhyloP100		0.26
Vest4		0.061
GERP RS		0.67
Mutation Taster		=186/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8191246; hg19: chr16-82132040;