8-38434748-C-A

Position:

• chr8-38434748-C-A

Variant summary

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

The NM_023110.3(FGFR1):​c.92-4800G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 159,242 control chromosomes in the GnomAD database, including 834 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 0.079 (796 hom., cov: 32)
  • Exomes 𝑓: 0.098 (38 hom.)
• Consequence: FGFR1 NM_023110.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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]

(HGNC:):

RPS20P22 (HGNC:36379): (ribosomal protein S20 pseudogene 22)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR1	NM_023110.3	c.92-4800G>T		intron_variant		ENST00000447712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1	ENST00000447712.7	c.92-4800G>T		intron_variant		1	NM_023110.3	P4
	ENST00000488192.1	n.917G>T		non_coding_transcript_exon_variant	1/1
RPS20P22	ENST00000473700.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12088 AN: 152122 Hom.: 794 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0975 AC: 683 AN: 7002 Hom.: 38 Cov.: 0 AF XY: 0.104 AC XY: 391 AN XY: 3754

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.00813

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.0852

Gnomad4 OTH exome AF: 0.0766

GnomAD4 genome AF: 0.0794 AC: 12093 AN: 152240 Hom.: 796 Cov.: 32 AF XY: 0.0870 AC XY: 6479 AN XY: 74434

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.0657

Alfa AF: 0.0812 Hom.: 92

Bravo AF: 0.0666

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.58

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: rs2956724; hg19: chr8-38292266;