ENST00000340624.9:c.-63-520G>A

Variant names:

• chr17-7629896-G-A
• rs3760213
• ENST00000340624.9:c.-63-520G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000340624.9(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 ENST00000340624.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 12 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=-0.83).
• 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 rank	MANE	Protein	UniProt
SHBG	NM_001040.5	c.-277G>A		upstream_gene_variant		ENST00000380450.9	NP_001031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000380450.9	c.-277G>A		upstream_gene_variant		1	NM_001040.5	ENSP00000369816.4

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

African (AFR) AF: 0.0259 AC: 1073 AN: 41490

American (AMR) AF: 0.0675 AC: 1031 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.116 AC: 598 AN: 5168

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4824

European-Finnish (FIN) AF: 0.0555 AC: 588 AN: 10588

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7706 AN: 67962

Other (OTH) AF: 0.0840 AC: 177 AN: 2106

Alfa AF: 0.0952 Hom.: 1041

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
PhyloP100		0.027
PromoterAI		0.010	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: rs3760213; hg19: chr17-7533214;