17-7630424-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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

Verdict is Benign. Variant got -11 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHBG	NM_001040.5	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	c.120C>T	p.His40=	synonymous_variant	2/8	1	NM_001040.5	P1

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 712 AN: 152152 Hom.: 4 Cov.: 32

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.: 2 AF XY: 0.00553 AC XY: 752 AN XY: 135902

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.: 44 Cov.: 32 AF XY: 0.00669 AC XY: 4863 AN XY: 727138

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.: 4 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74462

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.: 1

Bravo AF: 0.00468

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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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

Other links and lift over

dbSNP: rs9282846; hg19: chr17-7533742; COSMIC: COSV52647083; COSMIC: COSV52647083;