1-235557598-C-T

Variant names:

• chr1-235557598-C-T
• rs291353
• NM_001098722.2:c.100-5361G>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.100-5361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,886 control chromosomes in the GnomAD database, including 33,805 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 0.66 (33805 hom., cov: 29)
• Consequence: GNG4 NM_001098722.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 19 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG4	NM_001098722.2	c.100-5361G>A		intron_variant	Intron 3 of 3	ENST00000391854.7	NP_001092192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG4	ENST00000391854.7	c.100-5361G>A		intron_variant	Intron 3 of 3	1	NM_001098722.2	ENSP00000375727.2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99881 AN: 151770 Hom.: 33761 Cov.: 29

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.658 AC: 99986 AN: 151886 Hom.: 33805 Cov.: 29 AF XY: 0.661 AC XY: 49034 AN XY: 74230

African (AFR) AF: 0.787 AC: 32584 AN: 41406

American (AMR) AF: 0.674 AC: 10274 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4393 AN: 5158

South Asian (SAS) AF: 0.637 AC: 3045 AN: 4782

European-Finnish (FIN) AF: 0.644 AC: 6802 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39145 AN: 67934

Other (OTH) AF: 0.586 AC: 1238 AN: 2112

Alfa AF: 0.601 Hom.: 100984

Bravo AF: 0.667

Asia WGS AF: 0.724 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.58
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: rs291353; hg19: chr1-235720898;