chr17-7623644-G-T

Variant names:

• chr17-7623644-G-T
• rs9898876
• ENST00000575314.5:c.-61-6774G>T

Variant summary

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

The ENST00000575314.5(SHBG):​c.-61-6774G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,106 control chromosomes in the GnomAD database, including 2,406 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 0.18 (2406 hom., cov: 32)
• Consequence: SHBG ENST00000575314.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 20 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHBG	NM_001289114.2	c.-61-6774G>T		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.-61-6774G>T		intron_variant	Intron 1 of 7	1		ENSP00000458559.1
SHBG	ENST00000572262.5	c.-61-6774G>T		intron_variant	Intron 1 of 6	1		ENSP00000459999.1
SHBG	ENST00000574539.5	c.-61-6774G>T		intron_variant	Intron 1 of 6	1		ENSP00000458181.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26718 AN: 151988 Hom.: 2397 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.176 AC: 26737 AN: 152106 Hom.: 2406 Cov.: 32 AF XY: 0.171 AC XY: 12710 AN XY: 74362

African (AFR) AF: 0.190 AC: 7889 AN: 41466

American (AMR) AF: 0.136 AC: 2083 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.158 AC: 816 AN: 5168

South Asian (SAS) AF: 0.162 AC: 784 AN: 4830

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12752 AN: 67988

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.181 Hom.: 1165

Bravo AF: 0.181

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.53
PhyloP100		-0.88
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: rs9898876; hg19: chr17-7526962;