rs12150660

Positions:

• chr17-7618597-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SHBG	NM_001289114.2	c.-62+4486G>T		intron_variant			NP_001276043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000570547.5	c.-62+4486G>T		intron_variant		1		ENSP00000458875
SHBG	ENST00000572182.5	c.-62+4486G>T		intron_variant		1		ENSP00000458816
SHBG	ENST00000572262.5	c.-62+4486G>T		intron_variant		1		ENSP00000459999

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

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0838

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.181

Alfa AF: 0.224 Hom.: 1529

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12150660; hg19: chr17-7521915;