rs9324894

Positions:

• chr5-142686669-G-A

Variant summary

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

The ENST00000621536.4(FGF1):​c.-35+10953C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 151,976 control chromosomes in the GnomAD database, including 767 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 0.076 (767 hom., cov: 32)
• Consequence: FGF1 ENST00000621536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

Genes affected

FGF1 (HGNC:3665): (fibroblast growth factor 1) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF1	NM_001144934.2	c.-35+10953C>T		intron_variant
FGF1	NM_001144935.2	c.-35+11244C>T		intron_variant
FGF1	NM_001257205.1	c.-35+10953C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF1	ENST00000621536.4	c.-35+10953C>T		intron_variant		1		P1
FGF1	ENST00000494344.5	n.431+10953C>T		intron_variant, non_coding_transcript_variant		1
FGF1	ENST00000407758.5	c.-35+10953C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11506 AN: 151858 Hom.: 767 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0638

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

GnomAD4 genome AF: 0.0758 AC: 11517 AN: 151976 Hom.: 767 Cov.: 32 AF XY: 0.0773 AC XY: 5743 AN XY: 74298

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0202

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.0627

Alfa AF: 0.0522 Hom.: 76

Bravo AF: 0.0845

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9324894; hg19: chr5-142066234;