rs798489

Positions:

• chr7-2762169-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000275364.8(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 ENST00000275364.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GNA12	NM_007353.3	c.526-28668G>A		intron_variant		ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.526-28668G>A		intron_variant		1	NM_007353.3	ENSP00000275364	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30024 AN: 152144 Hom.: 3913 Cov.: 33

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.: 0 AF XY: 0.223 AC XY: 819 AN XY: 3670

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.197 AC: 30024 AN: 152262 Hom.: 3915 Cov.: 33 AF XY: 0.200 AC XY: 14877 AN XY: 74426

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.204

Alfa AF: 0.252 Hom.: 7602

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	12
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs798489; hg19: chr7-2801803; COSMIC: COSV51745942; COSMIC: COSV51745942;