1-235547476-C-T

Variant names:

• chr1-235547476-C-T
• rs6676353
• NM_001098722.2:c.*4633G>A

Variant summary

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

The NM_001098722.2(GNG4):​c.*4633G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,966 control chromosomes in the GnomAD database, including 24,212 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 0.56 (24212 hom., cov: 31)
• Consequence: GNG4 NM_001098722.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG4	NM_001098722.2	c.*4633G>A		downstream_gene_variant		ENST00000391854.7	NP_001092192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG4	ENST00000391854.7	c.*4633G>A		downstream_gene_variant		1	NM_001098722.2	ENSP00000375727.2
GNG4	ENST00000450593.5	c.*4633G>A		downstream_gene_variant		4		ENSP00000398629.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84410 AN: 151848 Hom.: 24199 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.556 AC: 84455 AN: 151966 Hom.: 24212 Cov.: 31 AF XY: 0.559 AC XY: 41493 AN XY: 74260

African (AFR) AF: 0.451 AC: 18720 AN: 41474

American (AMR) AF: 0.617 AC: 9429 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2093 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4282 AN: 5158

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6478 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39154 AN: 67926

Other (OTH) AF: 0.591 AC: 1243 AN: 2102

Alfa AF: 0.570 Hom.: 6233

Bravo AF: 0.554

Asia WGS AF: 0.647 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.55
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6676353; hg19: chr1-235710776; COSMIC: COSV63999088;