rs208354

Variant names:

• chr7-2741229-C-A
• rs208354
• NM_007353.3:c.526-7728G>T

Variant summary

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

The NM_007353.3(GNA12):​c.526-7728G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,184 control chromosomes in the GnomAD database, including 1,777 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 0.12 (1777 hom., cov: 32)
• Consequence: GNA12 NM_007353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA12	NM_007353.3	c.526-7728G>T		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.526-7728G>T		intron_variant	Intron 2 of 3	1	NM_007353.3	ENSP00000275364.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17712 AN: 152066 Hom.: 1778 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.116 AC: 17703 AN: 152184 Hom.: 1777 Cov.: 32 AF XY: 0.122 AC XY: 9055 AN XY: 74386

African (AFR) AF: 0.0256 AC: 1065 AN: 41552

American (AMR) AF: 0.123 AC: 1881 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2897 AN: 5152

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4816

European-Finnish (FIN) AF: 0.112 AC: 1181 AN: 10586

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8769 AN: 68002

Other (OTH) AF: 0.110 AC: 232 AN: 2112

Alfa AF: 0.121 Hom.: 1735

Bravo AF: 0.110

Asia WGS AF: 0.294 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-1.3
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: rs208354; hg19: chr7-2780863;