1-89384015-G-T

Variant names:

• chr1-89384015-G-T
• rs928655
• NM_198460.3:c.1469-78G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198460.3(GBP6):​c.1469-78G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000818 in 1,221,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: GBP6 NM_198460.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198460.3. 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
	GBP6	NM_198460.3	MANE Select	c.1469-78G>T		intron	N/A	NP_940862.2
	GBP6	NM_001320257.2		c.1079-78G>T		intron	N/A	NP_001307186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP6	ENST00000370456.5	TSL:1 MANE Select	c.1469-78G>T		intron	N/A	ENSP00000359485.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.18e-7 AC: 1 AN: 1221884 Hom.: 0 AF XY: 0.00000166 AC XY: 1 AN XY: 601510

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27166

American (AMR) AF: 0.00 AC: 0 AN: 22214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18786

East Asian (EAS) AF: 0.00 AC: 0 AN: 35882

South Asian (SAS) AF: 0.00 AC: 0 AN: 62418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4208

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 952504

Other (OTH) AF: 0.00 AC: 0 AN: 51380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.57
PhyloP100		-0.64

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: rs928655; hg19: chr1-89849574;