rs798502

chr7-2750246-A-Cchr7-2750246-A-G

Variant summary

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

The NM_007353.3(GNA12):c.526-16745T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,136 control chromosomes in the GnomAD database, including 5,068 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 0.24 (5068 hom., cov: 32)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA12	NM_007353.3	c.526-16745T>G		intron_variant		ENST00000275364.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8	c.526-16745T>G		intron_variant		1	NM_007353.3	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36530 AN: 152018 Hom.: 5065 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.240 AC: 36547 AN: 152136 Hom.: 5068 Cov.: 32 AF XY: 0.244 AC XY: 18113 AN XY: 74370

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.249

Alfa AF: 0.273 Hom.: 7542

Bravo AF: 0.229

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.3
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs798502; hg19: chr7-2789880;