NM_002007.4:c.444+63C>T

Variant names:

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

Variant summary

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

The NM_002007.4(FGF4):​c.444+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,387,618 control chromosomes in the GnomAD database, including 493,854 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 0.76 (45189 hom., cov: 32)
  • Exomes 𝑓: 0.85 (448665 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF4	NM_002007.4	c.444+63C>T		intron_variant	Intron 2 of 2	ENST00000168712.3	NP_001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF4	ENST00000168712.3	c.444+63C>T		intron_variant	Intron 2 of 2	1	NM_002007.4	ENSP00000168712.1
FGF4	ENST00000538040.1	n.421-476C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115112 AN: 152018 Hom.: 45179 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.848 AC: 1047956 AN: 1235482 Hom.: 448665 AF XY: 0.850 AC XY: 521987 AN XY: 614190

African (AFR) AF: 0.544 AC: 15912 AN: 29274

American (AMR) AF: 0.572 AC: 20344 AN: 35592

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 19282 AN: 22732

East Asian (EAS) AF: 0.702 AC: 26115 AN: 37186

South Asian (SAS) AF: 0.819 AC: 61693 AN: 75298

European-Finnish (FIN) AF: 0.872 AC: 42629 AN: 48914

Middle Eastern (MID) AF: 0.871 AC: 4574 AN: 5250

European-Non Finnish (NFE) AF: 0.877 AC: 814203 AN: 928860

Other (OTH) AF: 0.825 AC: 43204 AN: 52376

GnomAD4 genome AF: 0.757 AC: 115152 AN: 152136 Hom.: 45189 Cov.: 32 AF XY: 0.755 AC XY: 56144 AN XY: 74382

African (AFR) AF: 0.555 AC: 23025 AN: 41488

American (AMR) AF: 0.664 AC: 10160 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2910 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3540 AN: 5136

South Asian (SAS) AF: 0.804 AC: 3880 AN: 4828

European-Finnish (FIN) AF: 0.876 AC: 9292 AN: 10610

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59520 AN: 67988

Other (OTH) AF: 0.792 AC: 1669 AN: 2108

Alfa AF: 0.843 Hom.: 62672

Bravo AF: 0.729

Asia WGS AF: 0.740 AC: 2574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		0.021
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: rs2073464; hg19: chr11-69588729; COSMIC: COSV51450002;