rs7918118

Positions:

• chr10-996883-C-A
• chr10-996883-C-G
• chr10-996883-C-T

Variant summary

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

The NM_012341.3(GTPBP4):​c.461-325C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 291,188 control chromosomes in the GnomAD database, including 84,649 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 0.77 (45140 hom., cov: 31)
  • Exomes 𝑓: 0.75 (39509 hom.)
• Consequence: GTPBP4 NM_012341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

GTPBP4 (HGNC:21535): (GTP binding protein 4) GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. 'Active' in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTPBP4	NM_012341.3	c.461-325C>A		intron_variant		ENST00000360803.9
GTPBP4	XM_047424932.1	c.320-325C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTPBP4	ENST00000360803.9	c.461-325C>A		intron_variant		1	NM_012341.3	P1
GTPBP4	ENST00000360059.5	c.320-325C>A		intron_variant		5
GTPBP4	ENST00000491635.1	n.1015C>A		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116579 AN: 151972 Hom.: 45096 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.750 AC: 104334 AN: 139098 Hom.: 39509 Cov.: 0 AF XY: 0.754 AC XY: 55687 AN XY: 73812

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.812

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.767 AC: 116678 AN: 152090 Hom.: 45140 Cov.: 31 AF XY: 0.773 AC XY: 57519 AN XY: 74374

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.743

Alfa AF: 0.735 Hom.: 21283

Bravo AF: 0.766

Asia WGS AF: 0.854 AC: 2969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.51

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: rs7918118; hg19: chr10-1042823;