rs1062177

Positions:

• chr5-151805140-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005754.3(G3BP1):​c.*1049C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,470 control chromosomes in the GnomAD database, including 3,716 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 0.20 (3692 hom., cov: 32)
  • Exomes 𝑓: 0.34 (24 hom.)
• Consequence: G3BP1 NM_005754.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

Genes affected

G3BP1 (HGNC:30292): (G3BP stress granule assembly factor 1) This gene encodes one of the DNA-unwinding enzymes which prefers partially unwound 3'-tailed substrates and can also unwind partial RNA/DNA and RNA/RNA duplexes in an ATP-dependent fashion. This enzyme is a member of the heterogeneous nuclear RNA-binding proteins and is also an element of the Ras signal transduction pathway. It binds specifically to the Ras-GTPase-activating protein by associating with its SH3 domain. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G3BP1	NM_005754.3	c.*1049C>T		3_prime_UTR_variant	12/12	ENST00000356245.8	NP_005745.1
G3BP1	NM_198395.2	c.*1049C>T		3_prime_UTR_variant	12/12		NP_938405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G3BP1	ENST00000356245.8	c.*1049C>T		3_prime_UTR_variant	12/12	1	NM_005754.3	ENSP00000348578	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29921 AN: 151924 Hom.: 3695 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.342 AC: 147 AN: 430 Hom.: 24 Cov.: 0 AF XY: 0.326 AC XY: 84 AN XY: 258

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.197 AC: 29909 AN: 152040 Hom.: 3692 Cov.: 32 AF XY: 0.203 AC XY: 15075 AN XY: 74314

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.190

Alfa AF: 0.227 Hom.: 4042

Bravo AF: 0.181

Asia WGS AF: 0.303 AC: 1049 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.79

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: rs1062177; hg19: chr5-151184701;