chr7-2750246-A-C

Variant names:

• chr7-2750246-A-C
• rs798502
• NM_007353.3:c.526-16745T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 74 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GNA12	NM_007353.3	c.526-16745T>G		intron_variant	Intron 2 of 3	ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.526-16745T>G		intron_variant	Intron 2 of 3	1	NM_007353.3	ENSP00000275364.3

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

African (AFR) AF: 0.107 AC: 4436 AN: 41548

American (AMR) AF: 0.279 AC: 4271 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5166

South Asian (SAS) AF: 0.156 AC: 752 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3950 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19783 AN: 67948

Other (OTH) AF: 0.249 AC: 526 AN: 2112

Alfa AF: 0.271 Hom.: 17764

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
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs798502; hg19: chr7-2789880;