8-38414029-G-C

Variant names:

• chr8-38414029-G-C
• NM_023110.3:c.2187-6C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023110.3(FGFR1):​c.2187-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FGFR1 NM_023110.3 splice_region, intron
• Scores: Splicing: ADA: 0.02606
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1	NM_023110.3	c.2187-6C>G		splice_region_variant, intron_variant	Intron 16 of 17	ENST00000447712.7	NP_075598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR1	ENST00000447712.7	c.2187-6C>G		splice_region_variant, intron_variant	Intron 16 of 17	1	NM_023110.3	ENSP00000400162.2
FGFR1	ENST00000397091.9	c.2181-6C>G		splice_region_variant, intron_variant	Intron 16 of 17	1		ENSP00000380280.5
FGFR1	ENST00000397108.8	c.2181-6C>G		splice_region_variant, intron_variant	Intron 17 of 18	1		ENSP00000380297.4
FGFR1	ENST00000397113.6	c.2181-6C>G		splice_region_variant, intron_variant	Intron 16 of 17	2		ENSP00000380302.2
FGFR1	ENST00000356207.9	c.1920-6C>G		splice_region_variant, intron_variant	Intron 15 of 16	1		ENSP00000348537.5
FGFR1	ENST00000397103.5	c.1920-6C>G		splice_region_variant, intron_variant	Intron 14 of 15	5		ENSP00000380292.1
FGFR1	ENST00000326324.10	c.1914-6C>G		splice_region_variant, intron_variant	Intron 15 of 16	1		ENSP00000327229.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Uncertain	0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.026
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 26

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-38271547;