17-7630953-C-T

Position:

• chr17-7630953-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.393+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 1,283,478 control chromosomes in the GnomAD database, including 586,401 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 0.97 (70929 hom., cov: 30)
  • Exomes 𝑓: 0.95 (515472 hom.)
• Consequence: SHBG NM_001040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHBG	NM_001040.5	c.393+84C>T		intron_variant		ENST00000380450.9	NP_001031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000380450.9	c.393+84C>T		intron_variant		1	NM_001040.5	ENSP00000369816.4

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146786 AN: 152086 Hom.: 70868 Cov.: 30

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 0.955 AC: 1079840 AN: 1131274 Hom.: 515472 AF XY: 0.954 AC XY: 548656 AN XY: 575056

Gnomad4 AFR exome AF: 0.993

Gnomad4 AMR exome AF: 0.981

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.947

Gnomad4 FIN exome AF: 0.939

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.958

GnomAD4 genome AF: 0.965 AC: 146906 AN: 152204 Hom.: 70929 Cov.: 30 AF XY: 0.966 AC XY: 71860 AN XY: 74416

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.958

Alfa AF: 0.958 Hom.: 14472

Bravo AF: 0.969

Asia WGS AF: 0.983 AC: 3417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.78
DANN	Benign	0.91

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: rs858517; hg19: chr17-7534271;