rs2911422

Positions:

• chr16-82075869-C-G
• chr16-82075869-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002153.3(HSD17B2):​c.664+4742C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 148,816 control chromosomes in the GnomAD database, including 24,836 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 0.58 (24836 hom., cov: 25)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.664+4742C>G		intron_variant		ENST00000199936.9
HSD17B2	XM_047434049.1	c.664+4742C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.664+4742C>G		intron_variant		1	NM_002153.3	P1
HSD17B2-AS1	ENST00000567021.1	n.44-4680G>C		intron_variant, non_coding_transcript_variant		5
HSD17B2	ENST00000566838.2	c.292+4742C>G		intron_variant		2
HSD17B2	ENST00000568090.5	c.256+4742C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.575 AC: 85561 AN: 148712 Hom.: 24801 Cov.: 25

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.576 AC: 85656 AN: 148816 Hom.: 24836 Cov.: 25 AF XY: 0.574 AC XY: 41554 AN XY: 72400

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.538

Alfa AF: 0.575 Hom.: 3151

Bravo AF: 0.582

Asia WGS AF: 0.464 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.17
DANN	Benign	0.41

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: rs2911422; hg19: chr16-82109474;