17-7622230-C-G

Position:

• chr17-7622230-C-G

Variant summary

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

The ENST00000575314.5(SHBG):​c.-62+8119C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,472 control chromosomes in the GnomAD database, including 7,867 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 0.29 (7867 hom., cov: 28)
• Consequence: SHBG ENST00000575314.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHBG	NM_001289114.2	c.-62+8119C>G		intron_variant			NP_001276043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000570547.5	c.-62+8119C>G		intron_variant		1		ENSP00000458875
SHBG	ENST00000572182.5	c.-62+8119C>G		intron_variant		1		ENSP00000458816
SHBG	ENST00000572262.5	c.-62+8119C>G		intron_variant		1		ENSP00000459999

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44041 AN: 151354 Hom.: 7866 Cov.: 28

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.291 AC: 44044 AN: 151472 Hom.: 7867 Cov.: 28 AF XY: 0.295 AC XY: 21842 AN XY: 73986

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.328

Alfa AF: 0.187 Hom.: 397

Bravo AF: 0.269

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.2
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1017163; hg19: chr17-7525548; COSMIC: COSV52646455; COSMIC: COSV52646455;