rs12150660

Variant names:

• chr17-7618597-G-T
• rs12150660
• ENST00000575314.5:c.-62+4486G>T

Variant summary

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

The ENST00000575314.5(SHBG):​c.-62+4486G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,054 control chromosomes in the GnomAD database, including 2,808 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 0.17 (2808 hom., cov: 31)
• Consequence: SHBG ENST00000575314.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 55 publications found

Genes affected

SHBG (HGNC:10839): (sex hormone binding globulin) This gene encodes a steroid binding protein that was first described as a plasma protein secreted by the liver but is now thought to participate in the regulation of steroid responses. The encoded protein transports androgens and estrogens in the blood, binding each steroid molecule as a dimer formed from identical or nearly identical monomers. Polymorphisms in this gene have been associated with polycystic ovary syndrome and type 2 diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHBG	NM_001289114.2	c.-62+4486G>T		intron_variant	Intron 1 of 7		NP_001276043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000575314.5	c.-62+4486G>T		intron_variant	Intron 1 of 7	1		ENSP00000458559.1
SHBG	ENST00000572262.5	c.-62+4486G>T		intron_variant	Intron 1 of 6	1		ENSP00000459999.1
SHBG	ENST00000574539.5	c.-62+4486G>T		intron_variant	Intron 1 of 6	1		ENSP00000458181.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26042 AN: 151936 Hom.: 2809 Cov.: 31

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26031 AN: 152054 Hom.: 2808 Cov.: 31 AF XY: 0.168 AC XY: 12499 AN XY: 74324

African (AFR) AF: 0.0660 AC: 2740 AN: 41516

American (AMR) AF: 0.145 AC: 2215 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5174

South Asian (SAS) AF: 0.0838 AC: 404 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2621 AN: 10540

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16774 AN: 67952

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.215 Hom.: 2899

Bravo AF: 0.159

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12150660; hg19: chr17-7521915;