rs383711

Variant names:

• chr6-33206221-G-A
• rs383711
• NM_014234.5:c.694+45G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33206221-G-A
• chr6-33206221-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014234.5(HSD17B8):​c.694+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,601,390 control chromosomes in the GnomAD database, including 10,770 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 0.093 (1211 hom., cov: 31)
  • Exomes 𝑓: 0.086 (9559 hom.)
• Consequence: HSD17B8 NM_014234.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B8	NM_014234.5	c.694+45G>A		intron_variant	Intron 7 of 8	ENST00000374662.4	NP_055049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B8	ENST00000374662.4	c.694+45G>A		intron_variant	Intron 7 of 8	1	NM_014234.5	ENSP00000363794.3
HSD17B8	ENST00000469186.1	n.858+45G>A		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14202 AN: 152104 Hom.: 1200 Cov.: 31

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.106 AC: 25809 AN: 242872 AF XY: 0.103

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.0751

Gnomad ASJ exome AF: 0.0449

Gnomad EAS exome AF: 0.526

Gnomad FIN exome AF: 0.0790

Gnomad NFE exome AF: 0.0684

Gnomad OTH exome AF: 0.0866

GnomAD4 exome AF: 0.0859 AC: 124490 AN: 1449168 Hom.: 9559 Cov.: 28 AF XY: 0.0850 AC XY: 61322 AN XY: 721334

African (AFR) AF: 0.0880 AC: 2911 AN: 33090

American (AMR) AF: 0.0772 AC: 3404 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.0468 AC: 1213 AN: 25938

East Asian (EAS) AF: 0.525 AC: 20765 AN: 39560

South Asian (SAS) AF: 0.0808 AC: 6944 AN: 85922

European-Finnish (FIN) AF: 0.0771 AC: 4026 AN: 52244

Middle Eastern (MID) AF: 0.0698 AC: 400 AN: 5732

European-Non Finnish (NFE) AF: 0.0719 AC: 79307 AN: 1102692

Other (OTH) AF: 0.0922 AC: 5520 AN: 59876

GnomAD4 genome AF: 0.0934 AC: 14221 AN: 152222 Hom.: 1211 Cov.: 31 AF XY: 0.0952 AC XY: 7085 AN XY: 74424

African (AFR) AF: 0.0904 AC: 3753 AN: 41528

American (AMR) AF: 0.0832 AC: 1273 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0436 AC: 151 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2664 AN: 5164

South Asian (SAS) AF: 0.0890 AC: 429 AN: 4822

European-Finnish (FIN) AF: 0.0852 AC: 903 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4715 AN: 68016

Other (OTH) AF: 0.120 AC: 253 AN: 2112

Alfa AF: 0.0776 Hom.: 1249

Bravo AF: 0.0974

Asia WGS AF: 0.241 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs383711; hg19: chr6-33173998; COSMIC: COSV63002238; COSMIC: COSV63002238;