rs6674438

chr1-235575215-T-C

Variant summary

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

The NM_001098722.2(GNG4):c.99+8525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,150 control chromosomes in the GnomAD database, including 1,826 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 0.15 (1826 hom., cov: 32)
• Consequence: GNG4 NM_001098722.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

Genes affected

GNG4 (HGNC:4407): (G protein subunit gamma 4) Predicted to enable G-protein beta-subunit binding activity. Involved in negative regulation of cell growth. 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNG4	NM_001098722.2	c.99+8525A>G		intron_variant		ENST00000391854.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNG4	ENST00000391854.7	c.99+8525A>G		intron_variant		1	NM_001098722.2	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22286 AN: 152032 Hom.: 1821 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.147 AC: 22306 AN: 152150 Hom.: 1826 Cov.: 32 AF XY: 0.141 AC XY: 10511 AN XY: 74386

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0732

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.184

Alfa AF: 0.172 Hom.: 4929

Bravo AF: 0.149

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.50

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: rs6674438; hg19: chr1-235738515;