rs6674438

Variant names:

• chr1-235575215-T-C
• rs6674438
• NM_001098722.2:c.99+8525A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• 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 rank	MANE	Protein	UniProt
GNG4	NM_001098722.2	c.99+8525A>G		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.99+8525A>G		intron_variant	Intron 3 of 3	1	NM_001098722.2	ENSP00000375727.2

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

African (AFR) AF: 0.127 AC: 5277 AN: 41506

American (AMR) AF: 0.152 AC: 2326 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0732 AC: 353 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1171 AN: 10602

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11876 AN: 67980

Other (OTH) AF: 0.184 AC: 388 AN: 2114

Alfa AF: 0.168 Hom.: 7028

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
PhyloP100		0.38
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: rs6674438; hg19: chr1-235738515;