chr6-33207006-A-G

Variant names:

• chr6-33207006-A-G
• rs421446
• NM_014234.5:c.*352A>G

Variant summary

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

The NM_014234.5(HSD17B8):​c.*352A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,762 control chromosomes in the GnomAD database, including 8,553 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 0.32 (8553 hom., cov: 30)
• Consequence: HSD17B8 NM_014234.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

HSD17B8 (HGNC:3554): (hydroxysteroid 17-beta dehydrogenase 8) In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000288751 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B8	NM_014234.5	c.*352A>G		downstream_gene_variant		ENST00000374662.4	NP_055049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B8	ENST00000374662.4	c.*352A>G		downstream_gene_variant		1	NM_014234.5	ENSP00000363794.3
ENSG00000288751	ENST00000692840.1	n.*75T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48915 AN: 151644 Hom.: 8526 Cov.: 30

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.323 AC: 48987 AN: 151762 Hom.: 8553 Cov.: 30 AF XY: 0.324 AC XY: 23989 AN XY: 74148

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.347

Alfa AF: 0.292 Hom.: 11845

Bravo AF: 0.327

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs421446; hg19: chr6-33174783;