1-235549778-C-T

Variant names:

• chr1-235549778-C-T
• rs10754680
• NM_001098722.2:c.*2331G>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.*2331G>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 0.56 in 152,114 control chromosomes in the GnomAD database, including 24,484 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 (24483 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: GNG4 NM_004485.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.806 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.*2331G>A		3_prime_UTR	Exon 4 of 4	NP_001092192.1
	GNG4	NM_001098721.2		c.*2331G>A		3_prime_UTR	Exon 4 of 4	NP_001092191.1
	GNG4	NM_004485.4		c.*2331G>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.*2331G>A		3_prime_UTR	Exon 4 of 4	ENSP00000375727.2
	GNG4	ENST00000450593.5	TSL:4	c.*2331G>A		3_prime_UTR	Exon 4 of 4	ENSP00000398629.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85102 AN: 151990 Hom.: 24471 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AF: 0.00 AC: 0 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) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.560 AC: 85148 AN: 152110 Hom.: 24483 Cov.: 33 AF XY: 0.562 AC XY: 41811 AN XY: 74366

African (AFR) AF: 0.471 AC: 19545 AN: 41490

American (AMR) AF: 0.620 AC: 9487 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3464

East Asian (EAS) AF: 0.827 AC: 4288 AN: 5184

South Asian (SAS) AF: 0.487 AC: 2347 AN: 4824

European-Finnish (FIN) AF: 0.614 AC: 6491 AN: 10576

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

European-Non Finnish (NFE) AF: 0.574 AC: 39003 AN: 67964

Other (OTH) AF: 0.592 AC: 1249 AN: 2110

Alfa AF: 0.572 Hom.: 4329

Bravo AF: 0.559

Asia WGS AF: 0.636 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.59
PhyloP100		-1.1
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: rs10754680; hg19: chr1-235713078; COSMIC: COSV63999112; COSMIC: COSV63999112;