17-7629896-G-A

Position:

• chr17-7629896-G-A

Variant summary

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

The NM_001289113.2(SHBG):​c.-63-520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,084 control chromosomes in the GnomAD database, including 628 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 0.078 (628 hom., cov: 32)
• Consequence: SHBG NM_001289113.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHBG	NM_001289113.2	c.-63-520G>A		intron_variant			NP_001276042.1
SHBG	NM_001289114.2	c.-61-522G>A		intron_variant			NP_001276043.1
SHBG	NM_001289115.2	c.-63-520G>A		intron_variant			NP_001276044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000340624.9	c.-63-520G>A		intron_variant		1		ENSP00000345675.6
SHBG	ENST00000575314.5	c.-61-522G>A		intron_variant		1		ENSP00000458559.1
SHBG	ENST00000572262.5	c.-61-522G>A		intron_variant		1		ENSP00000459999.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11943 AN: 151966 Hom.: 628 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0849

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

GnomAD4 genome AF: 0.0785 AC: 11933 AN: 152084 Hom.: 628 Cov.: 32 AF XY: 0.0749 AC XY: 5565 AN XY: 74332

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0675

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0840

Alfa AF: 0.103 Hom.: 803

Bravo AF: 0.0815

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3760213; hg19: chr17-7533214;