12-26966684-T-G

Variant summary

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

The 12-26966684-T-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,990 control chromosomes in the GnomAD database, including 4,494 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 0.23 (4494 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: FGFR1OP2 NM_015633.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

Genes affected

FGFR1OP2 (HGNC:23098): (FGFR1 oncogene partner 2) Predicted to enable identical protein binding activity. Predicted to be involved in response to wounding. Predicted to act upstream of or within wound healing. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR1OP2	NM_015633.3			downstream_gene_variant		ENST00000229395.8
FGFR1OP2	NM_001171887.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1OP2	ENST00000229395.8			downstream_gene_variant		2	NM_015633.3
FGFR1OP2	ENST00000327214.5			downstream_gene_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35649 AN: 151872 Hom.: 4490 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.217

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.235 AC: 35674 AN: 151990 Hom.: 4494 Cov.: 31 AF XY: 0.235 AC XY: 17494 AN XY: 74294

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.220

Alfa AF: 0.187 Hom.: 1355

Bravo AF: 0.237

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2129091; hg19: chr12-27119617;