7-2763876-C-T

Position:

• chr7-2763876-C-T

Variant summary

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

The NM_007353.3(GNA12):​c.526-30375G>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

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA12	NM_007353.3	c.526-30375G>A		intron_variant		ENST00000275364.8	NP_031379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.526-30375G>A		intron_variant		1	NM_007353.3	ENSP00000275364	P1
AMZ1	ENST00000489665.1	n.551-836C>T		intron_variant, non_coding_transcript_variant		1
GNA12	ENST00000407904.7	c.349-30375G>A		intron_variant		2		ENSP00000385935
GNA12	ENST00000471281.5	n.427-30375G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.246

Alfa AF: 0.233 Hom.: 977

Bravo AF: 0.221

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.60

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: rs798485; hg19: chr7-2803510;