17-42553937-C-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000413.4(HSD17B1):c.539+50C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 1,486,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
HSD17B1
NM_000413.4 intron
NM_000413.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.51
Publications
14 publications found
Genes affected
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]
HSD17B1-AS1 (HGNC:55314): (HSD17B1 antisense RNA 1)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000413.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HSD17B1 | TSL:1 MANE Select | c.539+50C>G | intron | N/A | ENSP00000466799.1 | P14061 | |||
| HSD17B1 | TSL:2 | c.539+50C>G | intron | N/A | ENSP00000225929.5 | A0A0A0MQS7 | |||
| HSD17B1 | TSL:2 | n.922C>G | non_coding_transcript_exon | Exon 2 of 2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152132
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000150 AC: 2AN: 1334440Hom.: 0 Cov.: 20 AF XY: 0.00000150 AC XY: 1AN XY: 666614 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1334440
Hom.:
Cov.:
20
AF XY:
AC XY:
1
AN XY:
666614
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
30608
American (AMR)
AF:
AC:
0
AN:
39904
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25068
East Asian (EAS)
AF:
AC:
0
AN:
37240
South Asian (SAS)
AF:
AC:
0
AN:
80572
European-Finnish (FIN)
AF:
AC:
0
AN:
48736
Middle Eastern (MID)
AF:
AC:
0
AN:
5572
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1010748
Other (OTH)
AF:
AC:
0
AN:
55992
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74322 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152132
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
74322
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68010
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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