1-235586278-C-T

Position:

• chr1-235586278-C-T

Variant summary

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

The NM_001098722.2(GNG4):​c.-10-2430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,978 control chromosomes in the GnomAD database, including 13,590 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 0.41 (13590 hom., cov: 32)
• Consequence: GNG4 NM_001098722.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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 (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG4	NM_001098722.2	c.-10-2430G>A		intron_variant		ENST00000391854.7	NP_001092192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG4	ENST00000391854.7	c.-10-2430G>A		intron_variant		1	NM_001098722.2	ENSP00000375727	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62083 AN: 151860 Hom.: 13585 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.409 AC: 62128 AN: 151978 Hom.: 13590 Cov.: 32 AF XY: 0.420 AC XY: 31237 AN XY: 74304

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.348

Alfa AF: 0.380 Hom.: 5886

Bravo AF: 0.403

Asia WGS AF: 0.584 AC: 2032 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	0.89
DANN	Benign	0.66

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: rs2774339; hg19: chr1-235749578;