chr1-89063997-A-G

Variant names:

• chr1-89063997-A-G
• rs10493822
• NM_002053.3:c.-19-744T>C

Variant summary

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

The NM_002053.3(GBP1):​c.-19-744T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,006 control chromosomes in the GnomAD database, including 5,802 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 0.27 (5802 hom., cov: 31)
• Consequence: GBP1 NM_002053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002053.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	NM_002053.3	MANE Select	c.-19-744T>C		intron	N/A	NP_002044.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	ENST00000370473.5	TSL:1 MANE Select	c.-19-744T>C		intron	N/A	ENSP00000359504.4
	GBP1	ENST00000681280.1		c.-19-744T>C		intron	N/A	ENSP00000506404.1
	GBP1	ENST00000459831.2	TSL:3	n.202-744T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41434 AN: 151888 Hom.: 5798 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.273 AC: 41454 AN: 152006 Hom.: 5802 Cov.: 31 AF XY: 0.269 AC XY: 20005 AN XY: 74292

African (AFR) AF: 0.263 AC: 10884 AN: 41444

American (AMR) AF: 0.296 AC: 4514 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3468

East Asian (EAS) AF: 0.118 AC: 609 AN: 5178

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4812

European-Finnish (FIN) AF: 0.175 AC: 1852 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19899 AN: 67970

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.299 Hom.: 8668

Bravo AF: 0.282

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		2.4
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: rs10493822; hg19: chr1-89529680;