1-89064294-T-C

Variant names:

• chr1-89064294-T-C
• rs6682273
• NM_002053.3:c.-20+866A>G

Variant summary

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

The NM_002053.3(GBP1):​c.-20+866A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 147,184 control chromosomes in the GnomAD database, including 44,326 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 0.78 (44326 hom., cov: 23)
• Consequence: GBP1 NM_002053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 1 publications found

Genes affected

GBP1 (HGNC:4182): (guanylate binding protein 1) Guanylate binding protein expression is induced by interferon. Guanylate binding proteins are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP) and are distinguished from the GTP-binding proteins by the presence of 2 binding motifs rather than 3. [provided by RefSeq, Jul 2008]

ENSG00000307222 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.13).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3	c.-20+866A>G		intron_variant	Intron 1 of 10	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3208-3531T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.-20+866A>G		intron_variant	Intron 1 of 10	1	NM_002053.3	ENSP00000359504.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 114238 AN: 147078 Hom.: 44283 Cov.: 23

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.777 AC: 114333 AN: 147184 Hom.: 44326 Cov.: 23 AF XY: 0.775 AC XY: 55328 AN XY: 71410

African (AFR) AF: 0.815 AC: 32262 AN: 39580

American (AMR) AF: 0.670 AC: 9728 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2638 AN: 3448

East Asian (EAS) AF: 0.577 AC: 2788 AN: 4828

South Asian (SAS) AF: 0.785 AC: 3654 AN: 4652

European-Finnish (FIN) AF: 0.775 AC: 7420 AN: 9576

Middle Eastern (MID) AF: 0.747 AC: 215 AN: 288

European-Non Finnish (NFE) AF: 0.791 AC: 53256 AN: 67342

Other (OTH) AF: 0.781 AC: 1595 AN: 2042

Alfa AF: 0.779 Hom.: 5449

Bravo AF: 0.761

Asia WGS AF: 0.707 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.61
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: rs6682273; hg19: chr1-89529977;