rs2073464

Positions:

• chr11-69773961-G-A
• chr11-69773961-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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/exons	MANE	Protein	UniProt
FGF4	NM_002007.4	c.444+63C>T		intron_variant		ENST00000168712.3	NP_001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF4	ENST00000168712.3	c.444+63C>T		intron_variant		1	NM_002007.4	ENSP00000168712	P1
FGF4	ENST00000538040.1	n.421-476C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.877

Gnomad4 OTH exome AF: 0.825

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

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.792

Alfa AF: 0.864 Hom.: 50092

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073464; hg19: chr11-69588729; COSMIC: COSV51450002;