rs6257

Variant names:

• chr17-7630399-T-C
• rs6257
• ENST00000570527.5:n.*53T>C

Variant summary

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

The ENST00000570527.5(SHBG):​n.*53T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,612,454 control chromosomes in the GnomAD database, including 8,774 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 0.081 (590 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8184 hom.)
• Consequence: SHBG ENST00000570527.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 41 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHBG	NM_001040.5	c.112-17T>C		intron_variant	Intron 1 of 7	ENST00000380450.9	NP_001031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHBG	ENST00000380450.9	c.112-17T>C		intron_variant	Intron 1 of 7	1	NM_001040.5	ENSP00000369816.4

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12302 AN: 152058 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0894

GnomAD2 exomes AF: 0.0936 AC: 23539 AN: 251390 AF XY: 0.103

Gnomad AFR exome AF: 0.0519

Gnomad AMR exome AF: 0.0491

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0737

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.100 AC: 146468 AN: 1460278 Hom.: 8184 Cov.: 31 AF XY: 0.104 AC XY: 75436 AN XY: 726560

African (AFR) AF: 0.0514 AC: 1720 AN: 33458

American (AMR) AF: 0.0517 AC: 2310 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3092 AN: 26124

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39698

South Asian (SAS) AF: 0.184 AC: 15899 AN: 86202

European-Finnish (FIN) AF: 0.0756 AC: 4030 AN: 53334

Middle Eastern (MID) AF: 0.193 AC: 1110 AN: 5764

European-Non Finnish (NFE) AF: 0.101 AC: 112321 AN: 1110614

Other (OTH) AF: 0.0990 AC: 5975 AN: 60366

GnomAD4 genome AF: 0.0808 AC: 12303 AN: 152176 Hom.: 590 Cov.: 32 AF XY: 0.0805 AC XY: 5987 AN XY: 74386

African (AFR) AF: 0.0553 AC: 2294 AN: 41512

American (AMR) AF: 0.0616 AC: 942 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.170 AC: 822 AN: 4824

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10600

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6663 AN: 67994

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.0831 Hom.: 163

Bravo AF: 0.0755

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.68
PromoterAI		0.064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6257; hg19: chr17-7533717;