rs858518

Positions:

• chr17-7629707-G-A
• chr17-7629707-G-T

Variant summary

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

The ENST00000340624.9(SHBG):​c.-63-709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,990 control chromosomes in the GnomAD database, including 23,110 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 0.54 (23110 hom., cov: 32)
• Consequence: SHBG ENST00000340624.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHBG	NM_001289113.2	c.-63-709G>A		intron_variant
SHBG	NM_001289114.2	c.-61-711G>A		intron_variant
SHBG	NM_001289115.2	c.-63-709G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHBG	ENST00000340624.9	c.-63-709G>A		intron_variant		1
SHBG	ENST00000570547.5	c.-61-711G>A		intron_variant		1
SHBG	ENST00000572182.5	c.-61-711G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81567 AN: 151872 Hom.: 23083 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.537 AC: 81626 AN: 151990 Hom.: 23110 Cov.: 32 AF XY: 0.543 AC XY: 40340 AN XY: 74296

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.561

Alfa AF: 0.558 Hom.: 3018

Bravo AF: 0.536

Asia WGS AF: 0.550 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.5
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs858518; hg19: chr17-7533025; COSMIC: COSV52646475; COSMIC: COSV52646475;