rs16892645

chr4-15936769-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005130.5(FGFBP1):c.-20-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 624,684 control chromosomes in the GnomAD database, including 3,849 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 0.088 (880 hom., cov: 31)
  • Exomes 𝑓: 0.10 (2969 hom.)
• Consequence: FGFBP1 NM_005130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

FGFBP1 (HGNC:19695): (fibroblast growth factor binding protein 1) This gene encodes a secreted fibroblast growth factor carrier protein. The encoded protein plays a critical role in cell proliferation, differentiation and migration by binding to fibroblast growth factors and potentiating their biological effects on target cells. The encoded protein may also play a role in tumor growth as an angiogenic switch molecule, and expression of this gene has been associated with several types of cancer including pancreatic and colorectal adenocarcinoma. A pseudogene of this gene is also located on the short arm of chromosome 4. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFBP1	NM_005130.5	c.-20-117G>A		intron_variant		ENST00000382333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFBP1	ENST00000382333.2	c.-20-117G>A		intron_variant		3	NM_005130.5	P1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13328 AN: 152080 Hom.: 882 Cov.: 31

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.103 AC: 48780 AN: 472484 Hom.: 2969 AF XY: 0.106 AC XY: 26188 AN XY: 246796

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0576

Gnomad4 NFE exome AF: 0.0920

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0875 AC: 13323 AN: 152200 Hom.: 880 Cov.: 31 AF XY: 0.0897 AC XY: 6674 AN XY: 74420

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.0958

Alfa AF: 0.0996 Hom.: 798

Bravo AF: 0.0911

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.4
Dann	Benign	0.83

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: rs16892645; hg19: chr4-15938392; COSMIC: COSV52586360;