ENST00000585572.1:n.380-6193A>C

Variant names:

• chr17-42555426-A-C
• rs592389
• ENST00000585572.1:n.380-6193A>C

Variant summary

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

The ENST00000585572.1(ENSG00000266929):​n.380-6193A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,998 control chromosomes in the GnomAD database, including 25,524 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 0.57 (25524 hom., cov: 32)
• Consequence: ENSG00000266929 ENST00000585572.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

Genes affected

ENSG00000266929 (HGNC:):

HSD17B1 (HGNC:5210): (hydroxysteroid 17-beta dehydrogenase 1) This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B1	NM_000413.4	c.*488A>C		downstream_gene_variant		ENST00000585807.6	NP_000404.2
HSD17B1	NM_001330219.3	c.*488A>C		downstream_gene_variant			NP_001317148.1
HSD17B1	NR_144397.2	n.*212A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000266929	ENST00000585572.1	n.380-6193A>C		intron_variant	Intron 3 of 4	4
HSD17B1	ENST00000585807.6	c.*488A>C		downstream_gene_variant		1	NM_000413.4	ENSP00000466799.1
HSD17B1	ENST00000225929.5	c.*488A>C		downstream_gene_variant		2		ENSP00000225929.5

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87227 AN: 151880 Hom.: 25494 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.574 AC: 87313 AN: 151998 Hom.: 25524 Cov.: 32 AF XY: 0.570 AC XY: 42352 AN XY: 74274

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.526

Alfa AF: 0.564 Hom.: 7882

Bravo AF: 0.574

Asia WGS AF: 0.598 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs592389; hg19: chr17-40707444;