16-82035292-T-C

Position:

• chr16-82035292-T-C

Variant summary

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

The NM_002153.3(HSD17B2):​c.-133T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 733,832 control chromosomes in the GnomAD database, including 145,024 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 0.65 (32513 hom., cov: 30)
  • Exomes 𝑓: 0.62 (112511 hom.)
• Consequence: HSD17B2 NM_002153.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.-133T>C		5_prime_UTR_variant	1/5	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.-133T>C		5_prime_UTR_variant	1/4		XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936	c.-133T>C		5_prime_UTR_variant	1/5	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000566213.1	c.-133T>C		5_prime_UTR_variant	1/2	3		ENSP00000457943.1
HSD17B2	ENST00000563491.5	c.-144+144T>C		intron_variant		3		ENSP00000455992.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98851 AN: 151852 Hom.: 32464 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.617 AC: 358893 AN: 581862 Hom.: 112511 Cov.: 8 AF XY: 0.612 AC XY: 184959 AN XY: 301998

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.651 AC: 98955 AN: 151970 Hom.: 32513 Cov.: 30 AF XY: 0.654 AC XY: 48589 AN XY: 74262

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.614

Alfa AF: 0.627 Hom.: 31572

Bravo AF: 0.648

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.65

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: rs4445895; hg19: chr16-82068897; COSMIC: COSV52278744; COSMIC: COSV52278744;