5-142640943-T-G

Variant names:

• chr5-142640943-T-G
• rs12523624
• NM_000800.5:c.-34-26782A>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.-34-26782A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,794 control chromosomes in the GnomAD database, including 13,580 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 0.41 (13580 hom., cov: 32)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 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.-34-26782A>C		intron	N/A	NP_000791.1
	FGF1	NM_001144934.2		c.-34-26782A>C		intron	N/A	NP_001138406.1
	FGF1	NM_001144935.2		c.-34-26782A>C		intron	N/A	NP_001138407.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	ENST00000337706.7	TSL:2 MANE Select	c.-34-26782A>C		intron	N/A	ENSP00000338548.2
	FGF1	ENST00000612258.4	TSL:1	c.-34-26782A>C		intron	N/A	ENSP00000479024.1
	FGF1	ENST00000621536.4	TSL:1	c.-34-26782A>C		intron	N/A	ENSP00000480791.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61941 AN: 151676 Hom.: 13591 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.408 AC: 61924 AN: 151794 Hom.: 13580 Cov.: 32 AF XY: 0.407 AC XY: 30169 AN XY: 74190

African (AFR) AF: 0.255 AC: 10532 AN: 41266

American (AMR) AF: 0.389 AC: 5938 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1965 AN: 5158

South Asian (SAS) AF: 0.446 AC: 2144 AN: 4806

European-Finnish (FIN) AF: 0.472 AC: 4980 AN: 10554

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33578 AN: 67960

Other (OTH) AF: 0.399 AC: 842 AN: 2108

Alfa AF: 0.460 Hom.: 52233

Bravo AF: 0.395

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.48
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: rs12523624; hg19: chr5-142020508;