17-7630424-C-T

Variant names:

• chr17-7630424-C-T
• rs9282846
• ENST00000340624.9:c.-55C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001289113.2(SHBG):​c.-55C>T variant causes a 5 prime UTR premature start codon gain 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_001289113.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.17
• Publications: 2 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 -16 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 VariationId is 777024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289113.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	NM_001040.5	MANE Select	c.120C>T	p.His40His	synonymous	Exon 2 of 8	NP_001031.2
	SHBG	NM_001289113.2		c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001276042.1	I3L145
	SHBG	NM_001289114.2		c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001276043.1	I3L145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHBG	ENST00000340624.9	TSL:1	c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000345675.6	I3L145
	SHBG	ENST00000575314.5	TSL:1	c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000458559.1	I3L145
	SHBG	ENST00000572262.5	TSL:1	c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000459999.1	I3L2X4

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

GnomAD2 exomes AF: 0.00518 AC: 1303 AN: 251452 AF XY: 0.00553

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 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

African (AFR) AF: 0.00131 AC: 44 AN: 33472

American (AMR) AF: 0.00324 AC: 145 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00398 AC: 104 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00115 AC: 99 AN: 86248

European-Finnish (FIN) AF: 0.00326 AC: 174 AN: 53398

Middle Eastern (MID) AF: 0.00537 AC: 31 AN: 5768

European-Non Finnish (NFE) AF: 0.00816 AC: 9074 AN: 1111790

Other (OTH) AF: 0.00565 AC: 341 AN: 60388

GnomAD4 genome AF: 0.00468 AC: 712 AN: 152270 Hom.: 4 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74462

African (AFR) AF: 0.00171 AC: 71 AN: 41532

American (AMR) AF: 0.00451 AC: 69 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00753 AC: 512 AN: 68022

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.00682 Hom.: 3

Bravo AF: 0.00468

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.5
DANN	Benign	0.70
PhyloP100		1.2
PromoterAI		0.015	Neutral
Mutation Taster		=291/9	polymorphism

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

Other links and lift over

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