chr7-2735997-A-C

Variant names:

• chr7-2735997-A-C
• rs798525
• NM_007353.3:c.526-2496T>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.526-2496T>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
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	NM_007353.3	MANE Select	c.526-2496T>G		intron	N/A	NP_031379.2
	AMZ1	NM_001384740.1		c.949-2862A>C		intron	N/A	NP_001371669.1
	GNA12	NM_001293092.2		c.526-4247T>G		intron	N/A	NP_001280021.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	ENST00000275364.8	TSL:1 MANE Select	c.526-2496T>G		intron	N/A	ENSP00000275364.3	Q03113-1
	AMZ1	ENST00000489665.1	TSL:1	n.550+26181A>C		intron	N/A
	GNA12	ENST00000954395.1		c.604-2496T>G		intron	N/A	ENSP00000624454.1

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

African (AFR) AF: 0.524 AC: 21705 AN: 41432

American (AMR) AF: 0.631 AC: 9639 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1898 AN: 5150

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6175 AN: 10542

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42921 AN: 67964

Other (OTH) AF: 0.583 AC: 1227 AN: 2104

Alfa AF: 0.510 Hom.: 2018

Bravo AF: 0.588

Asia WGS AF: 0.542 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.28
PhyloP100		-2.6
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: rs798525; hg19: chr7-2775631;