rs4755731

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_024448571.2(HSD17B12):​c.-63+22584A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,052 control chromosomes in the GnomAD database, including 12,594 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 0.38 ( 12594 hom., cov: 32)

Consequence

HSD17B12
XM_024448571.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597
Variant links:
Genes affected
HSD17B12 (HGNC:18646): (hydroxysteroid 17-beta dehydrogenase 12) This gene encodes a very important 17beta-hydroxysteroid dehydrogenase (17beta-HSD) that converts estrone into estradiol in ovarian tissue. This enzyme is also involved in fatty acid elongation. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSD17B12XM_024448571.2 linkuse as main transcriptc.-63+22584A>G intron_variant XP_024304339.1
HSD17B12XM_024448572.2 linkuse as main transcriptc.-63+22584A>G intron_variant XP_024304340.1
HSD17B12XM_024448573.2 linkuse as main transcriptc.-63+22584A>G intron_variant XP_024304341.1
HSD17B12XM_047427074.1 linkuse as main transcriptc.-63+22584A>G intron_variant XP_047283030.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENSG00000283217ENST00000526615.6 linkuse as main transcriptn.287-9373A>G intron_variant 3
ENSG00000283341ENST00000529261.5 linkuse as main transcriptn.312-9373A>G intron_variant 3
ENSG00000283341ENST00000532864.6 linkuse as main transcriptn.281+22584A>G intron_variant 5
ENSG00000283217ENST00000533358.2 linkuse as main transcriptn.223-9373A>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.383
AC:
58162
AN:
151934
Hom.:
12586
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.197
Gnomad AMI
AF:
0.383
Gnomad AMR
AF:
0.545
Gnomad ASJ
AF:
0.260
Gnomad EAS
AF:
0.759
Gnomad SAS
AF:
0.425
Gnomad FIN
AF:
0.453
Gnomad MID
AF:
0.332
Gnomad NFE
AF:
0.423
Gnomad OTH
AF:
0.400
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.383
AC:
58191
AN:
152052
Hom.:
12594
Cov.:
32
AF XY:
0.391
AC XY:
29040
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.197
Gnomad4 AMR
AF:
0.546
Gnomad4 ASJ
AF:
0.260
Gnomad4 EAS
AF:
0.759
Gnomad4 SAS
AF:
0.424
Gnomad4 FIN
AF:
0.453
Gnomad4 NFE
AF:
0.423
Gnomad4 OTH
AF:
0.402
Alfa
AF:
0.413
Hom.:
6344
Bravo
AF:
0.383
Asia WGS
AF:
0.536
AC:
1861
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
8.3
DANN
Benign
0.90

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4755731; hg19: chr11-43685168; API