11-69774827-G-A

Variant names:

• chr11-69774827-G-A
• rs773272712
• NM_002007.4:c.258C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002007.4(FGF4):​c.258C>T​(p.Leu86Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L86L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FGF4 NM_002007.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.194 with no splicing effect.

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.258C>T	p.Leu86Leu	synonymous	Exon 1 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.258C>T	p.Leu86Leu	synonymous	Exon 1 of 3	ENSP00000168712.1	P08620-1
	FGF4	ENST00000538040.1	TSL:1	n.338C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1374246 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 680986

African (AFR) AF: 0.00 AC: 0 AN: 28476

American (AMR) AF: 0.00 AC: 0 AN: 35246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24184

East Asian (EAS) AF: 0.00 AC: 0 AN: 31790

South Asian (SAS) AF: 0.00 AC: 0 AN: 78272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5002

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078934

Other (OTH) AF: 0.00 AC: 0 AN: 57134

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.8
DANN	Benign	0.96
PhyloP100		-0.19

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: rs773272712; hg19: chr11-69589595;