NM_002053.3:c.-20+418G>A

Variant names:

• chr1-89064742-C-T
• rs12089335
• NM_002053.3:c.-20+418G>A

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+418G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,030 control chromosomes in the GnomAD database, including 9,231 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 0.34 (9231 hom., cov: 31)
• Consequence: GBP1 NM_002053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3	c.-20+418G>A		intron_variant	Intron 1 of 10	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3208-3083C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.-20+418G>A		intron_variant	Intron 1 of 10	1	NM_002053.3	ENSP00000359504.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51143 AN: 151912 Hom.: 9219 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.337 AC: 51194 AN: 152030 Hom.: 9231 Cov.: 31 AF XY: 0.331 AC XY: 24614 AN XY: 74298

African (AFR) AF: 0.472 AC: 19575 AN: 41460

American (AMR) AF: 0.322 AC: 4919 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1029 AN: 5170

South Asian (SAS) AF: 0.303 AC: 1458 AN: 4812

European-Finnish (FIN) AF: 0.176 AC: 1864 AN: 10574

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19960 AN: 67962

Other (OTH) AF: 0.332 AC: 702 AN: 2116

Alfa AF: 0.309 Hom.: 2622

Bravo AF: 0.356

Asia WGS AF: 0.272 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.78
PhyloP100		-3.2
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12089335; hg19: chr1-89530425;