rs3740640

Positions:

• chr11-69772815-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF4	NM_002007.4	c.*494A>G		3_prime_UTR_variant	3/3	ENST00000168712.3	NP_001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF4	ENST00000168712.3	c.*494A>G		3_prime_UTR_variant	3/3	1	NM_002007.4	ENSP00000168712	P1

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

GnomAD3 exomes AF: 0.0874 AC: 75 AN: 858 Hom.: 7 AF XY: 0.0764 AC XY: 37 AN XY: 484

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 SAS exome AF: 0.0513

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

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.0619

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.0815

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.121

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

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.109

Alfa AF: 0.123 Hom.: 514

Bravo AF: 0.118

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740640; hg19: chr11-69587583;