chr5-142598678-A-G

Variant names:

• chr5-142598678-A-G
• rs250092
• NM_000800.5:c.273+2024T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000800.5(FGF1):​c.273+2024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,222 control chromosomes in the GnomAD database, including 62,223 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 0.90 (62223 hom., cov: 31)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	NM_000800.5	MANE Select	c.273+2024T>C		intron	N/A	NP_000791.1
	FGF1	NM_001144892.3		c.273+2024T>C		intron	N/A	NP_001138364.1
	FGF1	NM_001144934.2		c.273+2024T>C		intron	N/A	NP_001138406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	ENST00000337706.7	TSL:2 MANE Select	c.273+2024T>C		intron	N/A	ENSP00000338548.2
	FGF1	ENST00000359370.10	TSL:1	c.273+2024T>C		intron	N/A	ENSP00000352329.6
	FGF1	ENST00000612258.4	TSL:1	c.273+2024T>C		intron	N/A	ENSP00000479024.1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137124 AN: 152104 Hom.: 62160 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.902 AC: 137246 AN: 152222 Hom.: 62223 Cov.: 31 AF XY: 0.903 AC XY: 67190 AN XY: 74426

African (AFR) AF: 0.976 AC: 40554 AN: 41554

American (AMR) AF: 0.925 AC: 14144 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3138 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5184

South Asian (SAS) AF: 0.965 AC: 4633 AN: 4802

European-Finnish (FIN) AF: 0.829 AC: 8789 AN: 10598

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57888 AN: 67998

Other (OTH) AF: 0.892 AC: 1882 AN: 2110

Alfa AF: 0.879 Hom.: 110477

Bravo AF: 0.912

Asia WGS AF: 0.984 AC: 3424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.4
DANN	Benign	0.51
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs250092; hg19: chr5-141978243;