rs6819187

Variant names:

• chr4-122873015-C-A
• rs6819187
• NM_001361665.2:c.179-3306C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-122873015-C-A
• chr4-122873015-C-G
• chr4-122873015-C-T

Variant summary

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

The NM_001361665.2(FGF2):​c.179-3306C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,106 control chromosomes in the GnomAD database, including 17,034 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 0.43 (17034 hom., cov: 33)
• Consequence: FGF2 NM_001361665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 3 publications found

Genes affected

FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF2	NM_001361665.2	c.179-3306C>A		intron_variant	Intron 1 of 2	ENST00000644866.2	NP_001348594.1
FGF2	NM_002006.6	c.578-3306C>A		intron_variant	Intron 1 of 2		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF2	ENST00000644866.2	c.179-3306C>A		intron_variant	Intron 1 of 2		NM_001361665.2	ENSP00000494222.1
FGF2	ENST00000264498.9	c.578-3306C>A		intron_variant	Intron 1 of 2	1		ENSP00000264498.4
FGF2	ENST00000608478.1	c.179-3306C>A		intron_variant	Intron 1 of 2	1		ENSP00000477134.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66097 AN: 151988 Hom.: 17029 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.435 AC: 66117 AN: 152106 Hom.: 17034 Cov.: 33 AF XY: 0.432 AC XY: 32123 AN XY: 74354

African (AFR) AF: 0.145 AC: 6034 AN: 41508

American (AMR) AF: 0.496 AC: 7584 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1635 AN: 3466

East Asian (EAS) AF: 0.493 AC: 2556 AN: 5180

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4812

European-Finnish (FIN) AF: 0.598 AC: 6318 AN: 10568

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38938 AN: 67970

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.484 Hom.: 2567

Bravo AF: 0.421

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.30
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: rs6819187; hg19: chr4-123794170;