rs6987534

chr8-38442197-G-Cchr8-38442197-G-T

Variant summary

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

The NM_023110.3(FGFR1):c.92-12249C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,926 control chromosomes in the GnomAD database, including 14,460 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 0.43 (14460 hom., cov: 31)
• Consequence: FGFR1 NM_023110.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR1	NM_023110.3	c.92-12249C>G		intron_variant		ENST00000447712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1	ENST00000447712.7	c.92-12249C>G		intron_variant		1	NM_023110.3	P4

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65645 AN: 151808 Hom.: 14443 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.432 AC: 65703 AN: 151926 Hom.: 14460 Cov.: 31 AF XY: 0.431 AC XY: 32021 AN XY: 74224

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.420

Alfa AF: 0.287 Hom.: 704

Bravo AF: 0.436

Asia WGS AF: 0.438 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.53

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: rs6987534; hg19: chr8-38299715;