rs928655

Positions:

• chr1-89384015-G-A
• chr1-89384015-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198460.3(GBP6):​c.1469-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,371,602 control chromosomes in the GnomAD database, including 372,240 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 0.66 (34902 hom., cov: 33)
  • Exomes 𝑓: 0.74 (337338 hom.)
• Consequence: GBP6 NM_198460.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

Genes affected

GBP6 (HGNC:25395): (guanylate binding protein family member 6) Guanylate-binding proteins, such as GBP6, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).[supplied by OMIM, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBP6	NM_198460.3	c.1469-78G>A		intron_variant		ENST00000370456.5
GBP6	NM_001320257.2	c.1079-78G>A		intron_variant
GBP6	XM_011540835.4	c.1469-78G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBP6	ENST00000370456.5	c.1469-78G>A		intron_variant		1	NM_198460.3	P1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100985 AN: 152004 Hom.: 34898 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.738 AC: 899766 AN: 1219480 Hom.: 337338 AF XY: 0.738 AC XY: 442891 AN XY: 600414

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.664 AC: 101015 AN: 152122 Hom.: 34902 Cov.: 33 AF XY: 0.661 AC XY: 49187 AN XY: 74368

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.678

Alfa AF: 0.746 Hom.: 87414

Bravo AF: 0.649

Asia WGS AF: 0.468 AC: 1628 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	0.052
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs928655; hg19: chr1-89849574; COSMIC: COSV65011548;