dbSNP rs1799941: SHBG:c.-68G>A (chr17-7630105-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000441599.6(SHBG):c.-68G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,358,172 control chromosomes in the GnomAD database, including 38,017 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 0.18 ( 3108 hom., cov: 32)

Exomes 𝑓: 0.23 ( 34909 hom. )

Consequence

SHBG
ENST00000441599.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

Publications

88 publications found

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

new If you want to explore the variant's impact on the transcript ENST00000441599.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441599.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SHBG	NM_001289113.2	c.-63-311G>A	intron	N/A	NP_001276042.1	I3L145
SHBG	NM_001289114.2	c.-61-313G>A	intron	N/A	NP_001276043.1	I3L145
SHBG	NM_001289115.2	c.-63-311G>A	intron	N/A	NP_001276044.1	P04278-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHBG	ENST00000441599.6	TSL:1	c.-68G>A	5_prime_UTR	Exon 1 of 6	ENSP00000393426.2	P04278-4
SHBG	ENST00000340624.9	TSL:1	c.-63-311G>A	intron	N/A	ENSP00000345675.6	I3L145
SHBG	ENST00000575314.5	TSL:1	c.-61-313G>A	intron	N/A	ENSP00000458559.1	I3L145

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27287

AN:

152008

Hom.:

3109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0663

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.229

AC:

275915

AN:

1206046

Hom.:

34909

Cov.:

AF XY:

0.226

AC XY:

138408

AN XY:

612260

show subpopulations

African (AFR)

AF:

0.0657

AC:

1868

AN:

28430

American (AMR)

AF:

0.107

AC:

4731

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4319

AN:

24560

East Asian (EAS)

AF:

0.000597

AC:

AN:

38554

South Asian (SAS)

AF:

0.104

AC:

8474

AN:

81112

European-Finnish (FIN)

AF:

0.269

AC:

13086

AN:

48692

Middle Eastern (MID)

AF:

0.200

AC:

866

AN:

4332

European-Non Finnish (NFE)

AF:

0.262

AC:

231719

AN:

884002

Other (OTH)

AF:

0.208

AC:

10829

AN:

52012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11572

23143

34715

46286

57858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6700

13400

20100

26800

33500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.179

AC:

27277

AN:

152126

Hom.:

3108

Cov.:

AF XY:

0.176

AC XY:

13110

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0661

AC:

2745

AN:

41524

American (AMR)

AF:

0.153

AC:

2331

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

583

AN:

3466

East Asian (EAS)

AF:

0.00212

AC:

AN:

5180

South Asian (SAS)

AF:

0.0923

AC:

445

AN:

4822

European-Finnish (FIN)

AF:

0.265

AC:

2803

AN:

10594

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17648

AN:

67960

Other (OTH)

AF:

0.189

AC:

396

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1089

2177

3266

4354

5443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.230

Hom.:

5543

Bravo

AF:

0.166

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

(source)

DANN

Benign

0.80

PhyloP100

0.13

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over