1-235549487-C-T

Variant names:

• chr1-235549487-C-T
• rs10754679
• NM_001098722.2:c.*2622G>A

Variant summary

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

The NM_004485.4(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_004485.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 4 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 = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004485.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG4	NM_001098722.2	MANE Select	c.*2622G>A		3_prime_UTR	Exon 4 of 4	NP_001092192.1
	GNG4	NM_001098721.2		c.*2622G>A		3_prime_UTR	Exon 4 of 4	NP_001092191.1
	GNG4	NM_004485.4		c.*2622G>A		3_prime_UTR	Exon 3 of 3	NP_004476.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG4	ENST00000391854.7	TSL:1 MANE Select	c.*2622G>A		3_prime_UTR	Exon 4 of 4	ENSP00000375727.2
	GNG4	ENST00000450593.5	TSL:4	c.*2622G>A		3_prime_UTR	Exon 4 of 4	ENSP00000398629.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 9 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.471 AC: 19506 AN: 41454

American (AMR) AF: 0.619 AC: 9446 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4291 AN: 5184

South Asian (SAS) AF: 0.486 AC: 2343 AN: 4818

European-Finnish (FIN) AF: 0.606 AC: 6399 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38976 AN: 67932

Other (OTH) AF: 0.593 AC: 1253 AN: 2112

Alfa AF: 0.567 Hom.: 37044

Bravo AF: 0.559

Asia WGS AF: 0.635 AC: 2209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.24
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: rs10754679; hg19: chr1-235712787;