11-69773961-G-C

Variant names:

• chr11-69773961-G-C
• rs2073464
• NM_002007.4:c.444+63C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002007.4(FGF4):​c.444+63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,236,820 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: FGF4 NM_002007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 9 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF4	NM_002007.4	MANE Select	c.444+63C>G		intron	N/A	NP_001998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF4	ENST00000168712.3	TSL:1 MANE Select	c.444+63C>G		intron	N/A	ENSP00000168712.1
	FGF4	ENST00000538040.1	TSL:1	n.421-476C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1236820 Hom.: 0 AF XY: 0.00000163 AC XY: 1 AN XY: 614830

African (AFR) AF: 0.00 AC: 0 AN: 29326

American (AMR) AF: 0.00 AC: 0 AN: 35650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22748

East Asian (EAS) AF: 0.0000538 AC: 2 AN: 37206

South Asian (SAS) AF: 0.00 AC: 0 AN: 75392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 929884

Other (OTH) AF: 0.00 AC: 0 AN: 52422

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 62672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		0.021

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: rs2073464; hg19: chr11-69588729;