Genetic Variant GNA12:c.526-28668G>A (chr7-2762169-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007353.3(GNA12):c.526-28668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 159,660 control chromosomes in the GnomAD database, including 4,141 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 0.20 ( 3915 hom., cov: 33)

Exomes 𝑓: 0.23 ( 226 hom. )

Consequence

GNA12
NM_007353.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.275

Publications

67 publications found

Variant links:

Genes affected

GNA12 (HGNC:4380): (G protein subunit alpha 12) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Involved in regulation of TOR signaling and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

GNA12 links:

AMZ1 (HGNC:22231): (archaelysin family metallopeptidase 1) Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

AMZ1 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA12	NM_007353.3 link	c.526-28668G>A		intron_variant	Intron 2 of 3	ENST00000275364.8	NP_031379.2	Q03113-1Q6ZQV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8 link	c.526-28668G>A		intron_variant	Intron 2 of 3	1	NM_007353.3	ENSP00000275364.3		Q03113-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

30024

AN:

152144

Hom.:

3913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0479

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.0867

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.225

AC:

1668

AN:

7398

Hom.:

226

Cov.:

AF XY:

0.223

AC XY:

819

AN XY:

3670

show subpopulations

African (AFR)

AF:

0.0268

AC:

AN:

298

American (AMR)

AF:

0.196

AC:

AN:

184

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

AN:

362

East Asian (EAS)

AF:

0.113

AC:

AN:

488

South Asian (SAS)

AF:

0.0625

AC:

AN:

European-Finnish (FIN)

AF:

0.298

AC:

AN:

238

Middle Eastern (MID)

AF:

0.107

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

1307

AN:

5226

Other (OTH)

AF:

0.209

AC:

103

AN:

494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.197

AC:

30024

AN:

152262

Hom.:

3915

Cov.:

AF XY:

0.200

AC XY:

14877

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0478

AC:

1987

AN:

41588

American (AMR)

AF:

0.227

AC:

3466

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3468

East Asian (EAS)

AF:

0.0848

AC:

440

AN:

5188

South Asian (SAS)

AF:

0.0870

AC:

420

AN:

4830

European-Finnish (FIN)

AF:

0.364

AC:

3851

AN:

10576

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.268

AC:

18253

AN:

67994

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1191

2383

3574

4766

5957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.247

Hom.:

16405

Bravo

AF:

0.181

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over