chr17-7630583-C-T

Position:

• chr17-7630583-C-T

Variant summary

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

The NM_001040.5(SHBG):​c.203+76C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 1,542,928 control chromosomes in the GnomAD database, including 6,488 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 0.095 (801 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5687 hom.)
• Consequence: SHBG NM_001040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHBG	NM_001040.5	c.203+76C>T		intron_variant		ENST00000380450.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHBG	ENST00000380450.9	c.203+76C>T		intron_variant		1	NM_001040.5	P1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14502 AN: 152054 Hom.: 799 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0837 AC: 116464 AN: 1390756 Hom.: 5687 Cov.: 22 AF XY: 0.0872 AC XY: 60701 AN XY: 695944

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0501

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0549

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0525

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0907

GnomAD4 genome AF: 0.0954 AC: 14518 AN: 152172 Hom.: 801 Cov.: 32 AF XY: 0.0949 AC XY: 7063 AN XY: 74404

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0771

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0775 Hom.: 506

Bravo AF: 0.0951

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.3
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9913778; hg19: chr17-7533901;