chr1-235549487-C-T

Position:

• chr1-235549487-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.*2622G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,012 control chromosomes in the GnomAD database, including 24,391 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 (24388 hom., cov: 31)
  • Exomes 𝑓: 0.56 (3 hom.)
• Consequence: GNG4 NM_001098722.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNG4	NM_001098722.2	c.*2622G>A		3_prime_UTR_variant	4/4	ENST00000391854.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNG4	ENST00000391854.7	c.*2622G>A		3_prime_UTR_variant	4/4	1	NM_001098722.2	P1
GNG4	ENST00000450593.5	c.*2622G>A		3_prime_UTR_variant	4/4	4		P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84915 AN: 151876 Hom.: 24377 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.563

GnomAD4 genome AF: 0.559 AC: 84958 AN: 151994 Hom.: 24388 Cov.: 31 AF XY: 0.561 AC XY: 41669 AN XY: 74290

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.593

Alfa AF: 0.561 Hom.: 4744

Bravo AF: 0.559

Asia WGS AF: 0.635 AC: 2209 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	1.9
DANN	Benign	0.67

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: rs10754679; hg19: chr1-235712787;