1-235550153-A-G

Variant names:

• chr1-235550153-A-G
• rs10925976
• NM_001098722.2:c.*1956T>C

Variant summary

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

The NM_001098722.2(GNG4):​c.*1956T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,062 control chromosomes in the GnomAD database, including 26,132 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 0.58 (26128 hom., cov: 32)
  • Exomes 𝑓: 0.80 (4 hom.)
• Consequence: GNG4 NM_001098722.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098722.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG4	NM_001098722.2	MANE Select	c.*1956T>C		3_prime_UTR	Exon 4 of 4	NP_001092192.1	P50150
	GNG4	NM_001098721.2		c.*1956T>C		3_prime_UTR	Exon 4 of 4	NP_001092191.1	B1APZ0
	GNG4	NM_004485.4		c.*1956T>C		3_prime_UTR	Exon 3 of 3	NP_004476.1	P50150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG4	ENST00000391854.7	TSL:1 MANE Select	c.*1956T>C		3_prime_UTR	Exon 4 of 4	ENSP00000375727.2	P50150
	GNG4	ENST00000450593.5	TSL:4	c.*1956T>C		3_prime_UTR	Exon 4 of 4	ENSP00000398629.1	P50150

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87998 AN: 151934 Hom.: 26115 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 4 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

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) AF: 0.750 AC: 6 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.579 AC: 88044 AN: 152052 Hom.: 26128 Cov.: 32 AF XY: 0.580 AC XY: 43126 AN XY: 74350

African (AFR) AF: 0.477 AC: 19772 AN: 41468

American (AMR) AF: 0.640 AC: 9770 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3468

East Asian (EAS) AF: 0.829 AC: 4279 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4820

European-Finnish (FIN) AF: 0.634 AC: 6706 AN: 10576

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41147 AN: 67974

Other (OTH) AF: 0.614 AC: 1293 AN: 2106

Alfa AF: 0.599 Hom.: 12806

Bravo AF: 0.579

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-0.52
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: rs10925976; hg19: chr1-235713453; COSMIC: COSV63999114; COSMIC: COSV63999114;