chr1-89054646-GAAAAAC-G

Variant names:

• chr1-89054646-GAAAAAC-G
• rs66614512
• NM_002053.3:c.1665+30_1665+35delGTTTTT

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP5 BA1

The NM_002053.3(GBP1):​c.1665+30_1665+35delGTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,587,236 control chromosomes in the GnomAD database, including 199,076 homozygotes. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (15467 hom., cov: 0)
  • Exomes 𝑓: 0.50 (183609 hom.)
• Consequence: GBP1 NM_002053.3 intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.196

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]

LOC105378841 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP5: Variant 1-89054646-GAAAAAC-G is Pathogenic according to our data. Variant chr1-89054646-GAAAAAC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1320035.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3	c.1665+30_1665+35delGTTTTT		intron_variant	Intron 10 of 10	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3207+7728_3207+7733delAAAACA		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.1665+30_1665+35delGTTTTT		intron_variant	Intron 10 of 10	1	NM_002053.3	ENSP00000359504.4

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66378 AN: 151382 Hom.: 15469 Cov.: 0

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.441

GnomAD3 exomes AF: 0.452 AC: 101974 AN: 225366 Hom.: 23947 AF XY: 0.461 AC XY: 55978 AN XY: 121386

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.481

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.501 AC: 719150 AN: 1435734 Hom.: 183609 AF XY: 0.503 AC XY: 359284 AN XY: 714756

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.603

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.438 AC: 66389 AN: 151502 Hom.: 15467 Cov.: 0 AF XY: 0.441 AC XY: 32680 AN XY: 74028

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.438

Alfa AF: 0.473 Hom.: 3310

Bravo AF: 0.409

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neutrophil inclusion bodies Pathogenic:1

-

Phenosystems SA

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs66614512; hg19: chr1-89520329;