chr17-7630583-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SHBGNM_001040.5 linkuse as main transcriptc.203+76C>T intron_variant ENST00000380450.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SHBGENST00000380450.9 linkuse as main transcriptc.203+76C>T intron_variant 1 NM_001040.5 P1P04278-1

Frequencies

GnomAD3 genomes
AF:
0.0954
AC:
14502
AN:
152054
Hom.:
799
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.149
Gnomad4 AMR exome
AF:
0.0501
Gnomad4 ASJ exome
AF:
0.122
Gnomad4 EAS exome
AF:
0.0549
Gnomad4 SAS exome
AF:
0.188
Gnomad4 FIN exome
AF:
0.0525
Gnomad4 NFE exome
AF:
0.0761
Gnomad4 OTH exome
AF:
0.0907
GnomAD4 genome
AF:
0.0954
AC:
14518
AN:
152172
Hom.:
801
Cov.:
32
AF XY:
0.0949
AC XY:
7063
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.142
Gnomad4 AMR
AF:
0.0668
Gnomad4 ASJ
AF:
0.126
Gnomad4 EAS
AF:
0.0431
Gnomad4 SAS
AF:
0.182
Gnomad4 FIN
AF:
0.0539
Gnomad4 NFE
AF:
0.0771
Gnomad4 OTH
AF:
0.0838
Alfa
AF:
0.0775
Hom.:
506
Bravo
AF:
0.0951
Asia WGS
AF:
0.133
AC:
462
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
3.3
DANN
Benign
0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9913778; hg19: chr17-7533901; API