17-7618382-T-C

Variant names:

• chr17-7618382-T-C
• rs2908809
• ENST00000575314.5:c.-62+4271T>C

Variant summary

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

The ENST00000575314.5(SHBG):​c.-62+4271T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,456 control chromosomes in the GnomAD database, including 18,302 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 0.48 (18302 hom., cov: 29)
• Consequence: SHBG ENST00000575314.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHBG	NM_001289114.2	c.-62+4271T>C		intron_variant	Intron 1 of 7		NP_001276043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000575314.5	c.-62+4271T>C		intron_variant	Intron 1 of 7	1		ENSP00000458559.1
SHBG	ENST00000572262.5	c.-62+4271T>C		intron_variant	Intron 1 of 6	1		ENSP00000459999.1
SHBG	ENST00000574539.5	c.-62+4271T>C		intron_variant	Intron 1 of 6	1		ENSP00000458181.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72286 AN: 151338 Hom.: 18292 Cov.: 29

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.478 AC: 72340 AN: 151456 Hom.: 18302 Cov.: 29 AF XY: 0.477 AC XY: 35267 AN XY: 73972

African (AFR) AF: 0.308 AC: 12728 AN: 41354

American (AMR) AF: 0.432 AC: 6578 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2245 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2168 AN: 5046

South Asian (SAS) AF: 0.637 AC: 3059 AN: 4800

European-Finnish (FIN) AF: 0.487 AC: 5104 AN: 10474

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38738 AN: 67788

Other (OTH) AF: 0.500 AC: 1051 AN: 2102

Alfa AF: 0.500 Hom.: 2358

Bravo AF: 0.464

Asia WGS AF: 0.513 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.23
PhyloP100		-1.5
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: rs2908809; hg19: chr17-7521700; COSMIC: COSV51520487; COSMIC: COSV51520487;