rs798525

Positions:

• chr7-2735997-A-C
• chr7-2735997-A-T

Variant summary

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

The NM_007353.3(GNA12):​c.526-2496T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,948 control chromosomes in the GnomAD database, including 26,190 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 0.58 (26190 hom., cov: 31)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA12	NM_007353.3	c.526-2496T>G		intron_variant		ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.526-2496T>G		intron_variant		1	NM_007353.3	ENSP00000275364	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88690 AN: 151830 Hom.: 26163 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.584 AC: 88762 AN: 151948 Hom.: 26190 Cov.: 31 AF XY: 0.579 AC XY: 42963 AN XY: 74248

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.583

Alfa AF: 0.510 Hom.: 1914

Bravo AF: 0.588

Asia WGS AF: 0.542 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.28

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: rs798525; hg19: chr7-2775631;