NM_002153.3:c.266-16177A>G

Variant names:

• chr16-82051993-A-G
• rs4243229
• NM_002153.3:c.266-16177A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002153.3(HSD17B2):​c.266-16177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 152,320 control chromosomes in the GnomAD database, including 69,792 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 0.96 (69792 hom., cov: 33)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.983 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.266-16177A>G		intron	N/A	NP_002144.1	P37059

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.266-16177A>G		intron	N/A	ENSP00000199936.4	P37059
	HSD17B2	ENST00000891334.1		c.266-16177A>G		intron	N/A	ENSP00000561393.1
	HSD17B2	ENST00000891335.1		c.266-16177A>G		intron	N/A	ENSP00000561394.1

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145511 AN: 152202 Hom.: 69749 Cov.: 33

Gnomad AFR AF: 0.905

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.963

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.956 AC: 145608 AN: 152320 Hom.: 69792 Cov.: 33 AF XY: 0.954 AC XY: 71034 AN XY: 74486

African (AFR) AF: 0.905 AC: 37607 AN: 41554

American (AMR) AF: 0.964 AC: 14755 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3460 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4236 AN: 5172

South Asian (SAS) AF: 0.927 AC: 4472 AN: 4822

European-Finnish (FIN) AF: 0.989 AC: 10516 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67326 AN: 68040

Other (OTH) AF: 0.961 AC: 2034 AN: 2116

Alfa AF: 0.981 Hom.: 128959

Bravo AF: 0.951

Asia WGS AF: 0.875 AC: 3043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.84
PhyloP100		0.026
Mutation Taster		=100/0	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: rs4243229; hg19: chr16-82085598;