5-142635824-C-T

Variant names:

• chr5-142635824-C-T
• rs249923
• NM_000800.5:c.-34-21663G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FGF1	NM_000800.5	c.-34-21663G>A		intron_variant	Intron 1 of 3	ENST00000337706.7	NP_000791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7	c.-34-21663G>A		intron_variant	Intron 1 of 3	2	NM_000800.5	ENSP00000338548.2

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

African (AFR) AF: 0.103 AC: 4278 AN: 41540

American (AMR) AF: 0.320 AC: 4891 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1085 AN: 5182

South Asian (SAS) AF: 0.304 AC: 1465 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4068 AN: 10572

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29264 AN: 67986

Other (OTH) AF: 0.299 AC: 631 AN: 2112

Alfa AF: 0.384 Hom.: 21704

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
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs249923; hg19: chr5-142015389;