17-7622230-C-G

Variant names:

• chr17-7622230-C-G
• rs1017163
• ENST00000575314.5:c.-62+8119C>G

Variant summary

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

The NM_001289114.2(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 NM_001289114.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289114.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	NM_001289114.2		c.-62+8119C>G		intron	N/A	NP_001276043.1	I3L145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	ENST00000575314.5	TSL:1	c.-62+8119C>G		intron	N/A	ENSP00000458559.1	I3L145
	SHBG	ENST00000572262.5	TSL:1	c.-62+8119C>G		intron	N/A	ENSP00000459999.1	I3L2X4
	SHBG	ENST00000574539.5	TSL:1	c.-62+8119C>G		intron	N/A	ENSP00000458181.1	P04278-2

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

African (AFR) AF: 0.0793 AC: 3279 AN: 41332

American (AMR) AF: 0.288 AC: 4369 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1452 AN: 5106

South Asian (SAS) AF: 0.477 AC: 2280 AN: 4778

European-Finnish (FIN) AF: 0.377 AC: 3939 AN: 10450

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26021 AN: 67884

Other (OTH) AF: 0.328 AC: 690 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.2
DANN	Benign	0.40
PhyloP100		0.24
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: rs1017163; hg19: chr17-7525548; COSMIC: COSV52646455; COSMIC: COSV52646455;