17-7630583-C-T

Variant names:

• chr17-7630583-C-T
• rs9913778
• NM_001040.5:c.203+76C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	NM_001040.5	MANE Select	c.203+76C>T		intron	N/A	NP_001031.2
	SHBG	NM_001146279.3		c.203+76C>T		intron	N/A	NP_001139751.1
	SHBG	NM_001289113.2		c.29+76C>T		intron	N/A	NP_001276042.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	ENST00000380450.9	TSL:1 MANE Select	c.203+76C>T		intron	N/A	ENSP00000369816.4
	SHBG	ENST00000340624.9	TSL:1	c.29+76C>T		intron	N/A	ENSP00000345675.6
	SHBG	ENST00000575314.5	TSL:1	c.29+76C>T		intron	N/A	ENSP00000458559.1

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

African (AFR) AF: 0.149 AC: 4769 AN: 32010

American (AMR) AF: 0.0501 AC: 2210 AN: 44068

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3128 AN: 25678

East Asian (EAS) AF: 0.0549 AC: 2161 AN: 39346

South Asian (SAS) AF: 0.188 AC: 15874 AN: 84484

European-Finnish (FIN) AF: 0.0525 AC: 2774 AN: 52846

Middle Eastern (MID) AF: 0.0850 AC: 479 AN: 5632

European-Non Finnish (NFE) AF: 0.0761 AC: 79799 AN: 1048620

Other (OTH) AF: 0.0907 AC: 5270 AN: 58072

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

African (AFR) AF: 0.142 AC: 5896 AN: 41490

American (AMR) AF: 0.0668 AC: 1021 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.0431 AC: 223 AN: 5180

South Asian (SAS) AF: 0.182 AC: 880 AN: 4824

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5241 AN: 67986

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0800 Hom.: 720

Bravo AF: 0.0951

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.3
DANN	Benign	0.70
PhyloP100		-1.7
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs9913778; hg19: chr17-7533901;