rs858517

Variant names:

• chr17-7630953-C-A
• rs858517
• NM_001040.5:c.393+84C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7630953-C-A
• chr17-7630953-C-G
• chr17-7630953-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040.5(SHBG):​c.393+84C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHBG NM_001040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040.5. 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_001040.5	MANE Select	c.393+84C>A		intron	N/A	NP_001031.2
	SHBG	NM_001146279.3		c.393+84C>A		intron	N/A	NP_001139751.1	P04278-5
	SHBG	NM_001289113.2		c.219+84C>A		intron	N/A	NP_001276042.1	I3L145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	ENST00000380450.9	TSL:1 MANE Select	c.393+84C>A		intron	N/A	ENSP00000369816.4	P04278-1
	SHBG	ENST00000340624.9	TSL:1	c.219+84C>A		intron	N/A	ENSP00000345675.6	I3L145
	SHBG	ENST00000575314.5	TSL:1	c.219+84C>A		intron	N/A	ENSP00000458559.1	I3L145

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1131636 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 575230

African (AFR) AF: 0.00 AC: 0 AN: 27318

American (AMR) AF: 0.00 AC: 0 AN: 40860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23538

East Asian (EAS) AF: 0.00 AC: 0 AN: 37742

South Asian (SAS) AF: 0.00 AC: 0 AN: 77390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3498

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 828202

Other (OTH) AF: 0.00 AC: 0 AN: 49382

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.62
DANN	Benign	0.91
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs858517; hg19: chr17-7534271;