rs1799941

Positions:

• chr17-7630105-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441599.6(SHBG):​c.-68G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,358,172 control chromosomes in the GnomAD database, including 38,017 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 0.18 (3108 hom., cov: 32)
  • Exomes 𝑓: 0.23 (34909 hom.)
• Consequence: SHBG ENST00000441599.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHBG	NM_001040.5			upstream_gene_variant		ENST00000380450.9	NP_001031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000380450.9			upstream_gene_variant		1	NM_001040.5	ENSP00000369816	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27287 AN: 152008 Hom.: 3109 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.229 AC: 275915 AN: 1206046 Hom.: 34909 Cov.: 17 AF XY: 0.226 AC XY: 138408 AN XY: 612260

Gnomad4 AFR exome AF: 0.0657

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.000597

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.179 AC: 27277 AN: 152126 Hom.: 3108 Cov.: 32 AF XY: 0.176 AC XY: 13110 AN XY: 74376

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0923

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.189

Alfa AF: 0.239 Hom.: 4456

Bravo AF: 0.166

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799941; hg19: chr17-7533423;