NM_002007.4:c.*494A>G

Variant names:

• chr11-69772815-T-C
• rs3740640
• NM_002007.4:c.*494A>G

Variant summary

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

The NM_002007.4(FGF4):​c.*494A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 174,644 control chromosomes in the GnomAD database, including 2,146 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 0.13 (1663 hom., cov: 33)
  • Exomes 𝑓: 0.17 (483 hom.)
• Consequence: FGF4 NM_002007.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 10 publications found

Genes affected

FGF4 (HGNC:3682): (fibroblast growth factor 4) 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 gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway. [provided by RefSeq, Jul 2008]

FGF4 Gene-Disease associations (from GenCC):

• thoracic malformation

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002007.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF4	NM_002007.4	MANE Select	c.*494A>G		3_prime_UTR	Exon 3 of 3	NP_001998.1	P08620-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF4	ENST00000168712.3	TSL:1 MANE Select	c.*494A>G		3_prime_UTR	Exon 3 of 3	ENSP00000168712.1	P08620-1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19753 AN: 152082 Hom.: 1663 Cov.: 33

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.0874 AC: 75 AN: 858 AF XY: 0.0764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0387

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.0769

GnomAD4 exome AF: 0.168 AC: 3777 AN: 22444 Hom.: 483 Cov.: 0 AF XY: 0.162 AC XY: 1724 AN XY: 10656

African (AFR) AF: 0.0518 AC: 31 AN: 598

American (AMR) AF: 0.0619 AC: 80 AN: 1292

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 120 AN: 1192

East Asian (EAS) AF: 0.400 AC: 1524 AN: 3814

South Asian (SAS) AF: 0.0815 AC: 38 AN: 466

European-Finnish (FIN) AF: 0.216 AC: 19 AN: 88

Middle Eastern (MID) AF: 0.0750 AC: 9 AN: 120

European-Non Finnish (NFE) AF: 0.133 AC: 1764 AN: 13292

Other (OTH) AF: 0.121 AC: 192 AN: 1582

GnomAD4 genome AF: 0.130 AC: 19764 AN: 152200 Hom.: 1663 Cov.: 33 AF XY: 0.135 AC XY: 10044 AN XY: 74412

African (AFR) AF: 0.0668 AC: 2776 AN: 41548

American (AMR) AF: 0.0842 AC: 1288 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2166 AN: 5168

South Asian (SAS) AF: 0.115 AC: 556 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2531 AN: 10584

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9669 AN: 67992

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.122 Hom.: 606

Bravo AF: 0.118

Asia WGS AF: 0.243 AC: 844 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	5.9
DANN	Benign	0.72
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3740640; hg19: chr11-69587583;