chr7-2763876-C-T

Variant names:

• chr7-2763876-C-T
• rs798485
• NM_007353.3:c.526-30375G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007353.3(GNA12):​c.526-30375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,118 control chromosomes in the GnomAD database, including 4,907 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 0.23 (4907 hom., cov: 32)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 19 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	NM_007353.3	MANE Select	c.526-30375G>A		intron	N/A	NP_031379.2
	GNA12	NM_001293092.2		c.525+31052G>A		intron	N/A	NP_001280021.1
	AMZ1	NM_001321766.2		c.949-836C>T		intron	N/A	NP_001308695.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA12	ENST00000275364.8	TSL:1 MANE Select	c.526-30375G>A		intron	N/A	ENSP00000275364.3
	AMZ1	ENST00000489665.1	TSL:1	n.551-836C>T		intron	N/A
	GNA12	ENST00000407904.7	TSL:2	c.349-30375G>A		intron	N/A	ENSP00000385935.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35638 AN: 152000 Hom.: 4906 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.234 AC: 35643 AN: 152118 Hom.: 4907 Cov.: 32 AF XY: 0.238 AC XY: 17698 AN XY: 74350

African (AFR) AF: 0.0989 AC: 4107 AN: 41516

American (AMR) AF: 0.277 AC: 4242 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1142 AN: 5152

South Asian (SAS) AF: 0.156 AC: 754 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4062 AN: 10570

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.288 AC: 19605 AN: 67988

Other (OTH) AF: 0.246 AC: 517 AN: 2104

Alfa AF: 0.196 Hom.: 1072

Bravo AF: 0.221

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.95
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: rs798485; hg19: chr7-2803510;