chr8-38459880-T-C

Position:

• chr8-38459880-T-C

Variant summary

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

The ENST00000447712.7(FGFR1):​c.-88-2346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,980 control chromosomes in the GnomAD database, including 28,926 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 0.60 (28926 hom., cov: 31)
• Consequence: FGFR1 ENST00000447712.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

FGFR1 (HGNC:3688): (fibroblast growth factor receptor 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR1	NM_023110.3	c.-88-2346A>G		intron_variant		ENST00000447712.7	NP_075598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR1	ENST00000447712.7	c.-88-2346A>G		intron_variant		1	NM_023110.3	ENSP00000400162	P4

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91506 AN: 151862 Hom.: 28904 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.602 AC: 91562 AN: 151980 Hom.: 28926 Cov.: 31 AF XY: 0.603 AC XY: 44778 AN XY: 74276

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.615

Alfa AF: 0.677 Hom.: 53921

Bravo AF: 0.590

Asia WGS AF: 0.592 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.63

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: rs7012413; hg19: chr8-38317398;