rs4243229

Positions:

• chr16-82051993-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.266-16177A>G		intron_variant		ENST00000199936.9
HSD17B2-AS1	XR_933797.3	n.3675-7385T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.266-16177A>G		intron_variant		1	NM_002153.3	P1
HSD17B2-AS1	ENST00000567021.1	n.592-7385T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.990

Gnomad4 OTH AF: 0.961

Alfa AF: 0.983 Hom.: 91908

Bravo AF: 0.951

Asia WGS AF: 0.875 AC: 3043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs4243229; hg19: chr16-82085598;