rs17531147

Positions:

• chr1-67720754-G-A
• chr1-67720754-G-T

Variant summary

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

The NM_018841.6(GNG12):​c.-26-13042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,156 control chromosomes in the GnomAD database, including 309 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 0.053 (309 hom., cov: 32)
• Consequence: GNG12 NM_018841.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

GNG12 (HGNC:19663): (G protein subunit gamma 12) Enables PDZ domain binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in extracellular exosome. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG12	NM_018841.6	c.-26-13042C>T		intron_variant		ENST00000370982.4	NP_061329.3
GNG12	XM_017001809.3	c.-26-13042C>T		intron_variant			XP_016857298.1
GNG12	XM_047425406.1	c.-26-13042C>T		intron_variant			XP_047281362.1
GNG12	XM_047425415.1	c.-26-13042C>T		intron_variant			XP_047281371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG12	ENST00000370982.4	c.-26-13042C>T		intron_variant		1	NM_018841.6	ENSP00000360021	P1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7996 AN: 152040 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0604

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

GnomAD4 genome AF: 0.0525 AC: 7991 AN: 152156 Hom.: 309 Cov.: 32 AF XY: 0.0490 AC XY: 3648 AN XY: 74394

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0598

Alfa AF: 0.0740 Hom.: 238

Bravo AF: 0.0526

Asia WGS AF: 0.0140 AC: 49 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.51

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: rs17531147; hg19: chr1-68186437;