XM_024448571.2:c.-63+22584A>G

Variant names:

• chr11-43663618-A-G
• rs4755731
• XM_024448571.2:c.-63+22584A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 6 publications found

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]

MIR670HG (HGNC:49204): (MIR670 host gene)

ENSG00000283341 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526615.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR670HG	ENST00000526615.6	TSL:3	n.287-9373A>G		intron	N/A
	ENSG00000283341	ENST00000529261.5	TSL:3	n.312-9373A>G		intron	N/A
	ENSG00000283341	ENST00000532864.6	TSL:5	n.281+22584A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58162 AN: 151934 Hom.: 12586 Cov.: 32

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

African (AFR) AF: 0.197 AC: 8169 AN: 41502

American (AMR) AF: 0.546 AC: 8332 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3468

East Asian (EAS) AF: 0.759 AC: 3912 AN: 5156

South Asian (SAS) AF: 0.424 AC: 2047 AN: 4828

European-Finnish (FIN) AF: 0.453 AC: 4783 AN: 10554

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28751 AN: 67970

Other (OTH) AF: 0.402 AC: 850 AN: 2114

Alfa AF: 0.413 Hom.: 6986

Bravo AF: 0.383

Asia WGS AF: 0.536 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.90
PhyloP100		0.60

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4755731;

hg19: chr11-43685168;