5-142595502-A-C

Position:

• chr5-142595502-A-C

Variant summary

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

The NM_000800.5(FGF1):​c.274-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,605,964 control chromosomes in the GnomAD database, including 181,433 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 0.53 (22746 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158687 hom.)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF1	NM_000800.5	c.274-18T>G		intron_variant		ENST00000337706.7	NP_000791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7	c.274-18T>G		intron_variant		2	NM_000800.5	ENSP00000338548	P1
SPRY4-AS1	ENST00000443800.5	n.356+13588A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80852 AN: 151882 Hom.: 22696 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.515

GnomAD3 exomes AF: 0.481 AC: 117529 AN: 244134 Hom.: 29275 AF XY: 0.479 AC XY: 63329 AN XY: 132162

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.634

Gnomad SAS exome AF: 0.470

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.463 AC: 673165 AN: 1453964 Hom.: 158687 Cov.: 30 AF XY: 0.463 AC XY: 334957 AN XY: 723116

Gnomad4 AFR exome AF: 0.738

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.533 AC: 80963 AN: 152000 Hom.: 22746 Cov.: 32 AF XY: 0.532 AC XY: 39501 AN XY: 74282

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.516

Alfa AF: 0.462 Hom.: 27852

Bravo AF: 0.536

Asia WGS AF: 0.544 AC: 1895 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	3.6
DANN	Benign	0.78

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: rs34003; hg19: chr5-141975067; COSMIC: COSV61803641;