chr8-38445447-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023110.3(FGFR1):​c.91+11909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,054 control chromosomes in the GnomAD database, including 4,064 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 ( 4064 hom., cov: 31)

Consequence

FGFR1
NM_023110.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGFR1NM_023110.3 linkuse as main transcriptc.91+11909G>A intron_variant ENST00000447712.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGFR1ENST00000447712.7 linkuse as main transcriptc.91+11909G>A intron_variant 1 NM_023110.3 P4P11362-1

Frequencies

GnomAD3 genomes
AF:
0.226
AC:
34292
AN:
151936
Hom.:
4054
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.281
Gnomad AMI
AF:
0.0921
Gnomad AMR
AF:
0.213
Gnomad ASJ
AF:
0.161
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.188
Gnomad FIN
AF:
0.204
Gnomad MID
AF:
0.165
Gnomad NFE
AF:
0.211
Gnomad OTH
AF:
0.204
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.226
AC:
34345
AN:
152054
Hom.:
4064
Cov.:
31
AF XY:
0.224
AC XY:
16661
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.282
Gnomad4 AMR
AF:
0.212
Gnomad4 ASJ
AF:
0.161
Gnomad4 EAS
AF:
0.168
Gnomad4 SAS
AF:
0.188
Gnomad4 FIN
AF:
0.204
Gnomad4 NFE
AF:
0.211
Gnomad4 OTH
AF:
0.205
Alfa
AF:
0.208
Hom.:
6791
Bravo
AF:
0.225
Asia WGS
AF:
0.186
AC:
646
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.13
DANN
Benign
0.36

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6474354; hg19: chr8-38302965; API