1-89125399-T-G

Variant names:

• chr1-89125399-T-G
• rs10754261
• NM_004120.5:c.-18+464A>C

Variant summary

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

The NM_004120.5(GBP2):​c.-18+464A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,032 control chromosomes in the GnomAD database, including 29,833 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 0.62 (29833 hom., cov: 31)
• Consequence: GBP2 NM_004120.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP2	NM_004120.5	c.-18+464A>C		intron_variant	Intron 1 of 10	ENST00000370466.4	NP_004111.2
LOC112268267	XR_007066213.1	n.*168T>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP2	ENST00000370466.4	c.-18+464A>C		intron_variant	Intron 1 of 10	1	NM_004120.5	ENSP00000359497.3
GBP2	ENST00000464839.5	n.-18+464A>C		intron_variant	Intron 4 of 14	2		ENSP00000434282.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93777 AN: 151914 Hom.: 29818 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.618

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.617 AC: 93822 AN: 152032 Hom.: 29833 Cov.: 31 AF XY: 0.624 AC XY: 46405 AN XY: 74342

African (AFR) AF: 0.459 AC: 19022 AN: 41436

American (AMR) AF: 0.637 AC: 9741 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4037 AN: 5150

South Asian (SAS) AF: 0.663 AC: 3195 AN: 4816

European-Finnish (FIN) AF: 0.798 AC: 8450 AN: 10588

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45301 AN: 67978

Other (OTH) AF: 0.613 AC: 1290 AN: 2104

Alfa AF: 0.641 Hom.: 11196

Bravo AF: 0.597

Asia WGS AF: 0.666 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		-0.21
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: rs10754261; hg19: chr1-89591082; COSMIC: COSV65068899;