Variant 17-7630424-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001040.5(SHBG):c.120C>T(p.His40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00665 in 1,613,894 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 44 hom. )

Consequence

SHBG
NM_001040.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.17

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]

SHBG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-7630424-C-T is Benign according to our data. Variant chr17-7630424-C-T is described in ClinVar as [Benign]. Clinvar id is 777024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHBG	NM_001040.5 linkuse as main transcript	c.120C>T	p.His40=	synonymous_variant	2/8	ENST00000380450.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHBG	ENST00000380450.9 linkuse as main transcript	c.120C>T	p.His40=	synonymous_variant	2/8	1	NM_001040.5	P1	P04278-1

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

712

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00753

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00518

AC:

1303

AN:

251452

Hom.:

AF XY:

0.00553

AC XY:

752

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00264

Gnomad NFE exome

AF:

0.00896

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00685

AC:

10013

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

4863

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00326

Gnomad4 NFE exome

AF:

0.00816

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00468

AC:

712

AN:

152270

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

326

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00739

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.5

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over