chr5-142611975-C-T

Variant names:

• chr5-142611975-C-T
• rs7727832
• NM_000800.5:c.169+1984G>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.169+1984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,244 control chromosomes in the GnomAD database, including 1,132 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 0.097 (1132 hom., cov: 32)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.208 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.169+1984G>A		intron	N/A	NP_000791.1
	FGF1	NM_001144892.3		c.169+1984G>A		intron	N/A	NP_001138364.1
	FGF1	NM_001144934.2		c.169+1984G>A		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.169+1984G>A		intron	N/A	ENSP00000338548.2
	FGF1	ENST00000359370.10	TSL:1	c.169+1984G>A		intron	N/A	ENSP00000352329.6
	FGF1	ENST00000612258.4	TSL:1	c.169+1984G>A		intron	N/A	ENSP00000479024.1

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14711 AN: 152126 Hom.: 1131 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0886

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.0968 AC: 14741 AN: 152244 Hom.: 1132 Cov.: 32 AF XY: 0.0947 AC XY: 7053 AN XY: 74452

African (AFR) AF: 0.212 AC: 8794 AN: 41516

American (AMR) AF: 0.0612 AC: 937 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0886 AC: 307 AN: 3464

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4822

European-Finnish (FIN) AF: 0.0594 AC: 630 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0523 AC: 3556 AN: 68016

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0765 Hom.: 180

Bravo AF: 0.102

Asia WGS AF: 0.0320 AC: 112 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	0.89
DANN	Benign	0.79
PhyloP100		-0.89
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: rs7727832; hg19: chr5-141991540;