5-142635824-C-T

Variant summary

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

The NM_000800.5(FGF1):c.-34-21663G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,178 control chromosomes in the GnomAD database, including 8,893 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 0.31 (8893 hom., cov: 33)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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]

SPRY4-AS1 (HGNC:53465): (SPRY4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF1	NM_000800.5	c.-34-21663G>A		intron_variant		ENST00000337706.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF1	ENST00000337706.7	c.-34-21663G>A		intron_variant		2	NM_000800.5	P1
SPRY4-AS1	ENST00000443800.5	n.357-35968C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47373 AN: 152060 Hom.: 8894 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.311 AC: 47357 AN: 152178 Hom.: 8893 Cov.: 33 AF XY: 0.307 AC XY: 22818 AN XY: 74386

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.299

Alfa AF: 0.397 Hom.: 16276

Bravo AF: 0.298

Asia WGS AF: 0.235 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.4
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs249923; hg19: chr5-142015389;