rs4755731

Variant names:

• chr11-43663618-A-G
• rs4755731
• ENST00000526615.6:n.287-9373A>G

Variant summary

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

The ENST00000526615.6(MIR670HG):​n.287-9373A>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: MIR670HG ENST00000526615.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 6 publications found

Genes affected

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

ENSG00000283341 (HGNC:):

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B12	XM_024448571.2	c.-63+22584A>G		intron_variant	Intron 3 of 12		XP_024304339.1
HSD17B12	XM_024448572.2	c.-63+22584A>G		intron_variant	Intron 3 of 12		XP_024304340.1
HSD17B12	XM_024448573.2	c.-63+22584A>G		intron_variant	Intron 4 of 13		XP_024304341.1
HSD17B12	XM_047427074.1	c.-63+22584A>G		intron_variant	Intron 3 of 12		XP_047283030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR670HG	ENST00000526615.6	n.287-9373A>G		intron_variant	Intron 4 of 4	3
ENSG00000283341	ENST00000529261.5	n.312-9373A>G		intron_variant	Intron 2 of 9	3
ENSG00000283341	ENST00000532864.6	n.281+22584A>G		intron_variant	Intron 3 of 10	5

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 v4.3

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

Other links and lift over

dbSNP: rs4755731; hg19: chr11-43685168;