rs858518

Variant names:

• chr17-7629707-G-A
• rs858518
• ENST00000340624.9:c.-63-709G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.74).
• 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 rank	MANE	Protein	UniProt
SHBG	NM_001289113.2	c.-63-709G>A		intron_variant	Intron 1 of 7		NP_001276042.1
SHBG	NM_001289114.2	c.-61-711G>A		intron_variant	Intron 1 of 7		NP_001276043.1
SHBG	NM_001289115.2	c.-63-709G>A		intron_variant	Intron 1 of 6		NP_001276044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000340624.9	c.-63-709G>A		intron_variant	Intron 1 of 7	1		ENSP00000345675.6
SHBG	ENST00000575314.5	c.-61-711G>A		intron_variant	Intron 1 of 7	1		ENSP00000458559.1
SHBG	ENST00000572262.5	c.-61-711G>A		intron_variant	Intron 1 of 6	1		ENSP00000459999.1

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

African (AFR) AF: 0.362 AC: 15022 AN: 41442

American (AMR) AF: 0.682 AC: 10412 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1802 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3741 AN: 5160

South Asian (SAS) AF: 0.424 AC: 2041 AN: 4818

European-Finnish (FIN) AF: 0.639 AC: 6757 AN: 10580

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40010 AN: 67932

Other (OTH) AF: 0.561 AC: 1184 AN: 2112

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
PhyloP100		-0.26
PromoterAI		-0.024	Neutral
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: rs858518; hg19: chr17-7533025; COSMIC: COSV52646475; COSMIC: COSV52646475;