rs6428503

Positions:

• chr1-89118386-T-C

Variant summary

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

The NM_004120.5(GBP2):​c.429-613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,114 control chromosomes in the GnomAD database, including 13,528 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 0.40 (13525 hom., cov: 32)
  • Exomes 𝑓: 0.41 (3 hom.)
• Consequence: GBP2 NM_004120.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

Genes affected

GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

LOC112268267 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP2	NM_004120.5	c.429-613A>G		intron_variant		ENST00000370466.4	NP_004111.2
LOC112268267	XR_007066213.1	n.265+344T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBP2	ENST00000370466.4	c.429-613A>G		intron_variant		1	NM_004120.5	ENSP00000359497	P1
GBP2	ENST00000463660.1	n.1835A>G		non_coding_transcript_exon_variant	1/5	2
GBP2	ENST00000464839.5	c.429-613A>G		intron_variant, NMD_transcript_variant		2		ENSP00000434282

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60518 AN: 151962 Hom.: 13528 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.412 AC: 14 AN: 34 Hom.: 3 Cov.: 0 AF XY: 0.333 AC XY: 8 AN XY: 24

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.398 AC: 60511 AN: 152080 Hom.: 13525 Cov.: 32 AF XY: 0.402 AC XY: 29913 AN XY: 74352

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.403

Alfa AF: 0.464 Hom.: 22635

Bravo AF: 0.366

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.76

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: rs6428503; hg19: chr1-89584069; COSMIC: COSV65068874;