NM_005130.5:c.*466G>A

Variant names:

• chr4-15935462-C-T
• rs732245
• NM_005130.5:c.*466G>A

Variant summary

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

The NM_005130.5(FGFBP1):​c.*466G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,888 control chromosomes in the GnomAD database, including 13,945 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 0.41 (13877 hom., cov: 33)
  • Exomes 𝑓: 0.40 (68 hom.)
• Consequence: FGFBP1 NM_005130.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFBP1	NM_005130.5	c.*466G>A		downstream_gene_variant		ENST00000382333.2	NP_005121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFBP1	ENST00000382333.2	c.*466G>A		downstream_gene_variant		3	NM_005130.5	ENSP00000371770.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62573 AN: 151956 Hom.: 13866 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.402 AC: 327 AN: 814 Hom.: 68 AF XY: 0.366 AC XY: 145 AN XY: 396

African (AFR) AF: 0.167 AC: 4 AN: 24

American (AMR) AF: 0.500 AC: 21 AN: 42

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 9 AN: 28

East Asian (EAS) AF: 0.750 AC: 6 AN: 8

South Asian (SAS) AF: 0.167 AC: 3 AN: 18

European-Finnish (FIN) AF: 0.550 AC: 22 AN: 40

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.398 AC: 245 AN: 616

Other (OTH) AF: 0.447 AC: 17 AN: 38

GnomAD4 genome AF: 0.412 AC: 62600 AN: 152074 Hom.: 13877 Cov.: 33 AF XY: 0.417 AC XY: 30978 AN XY: 74318

African (AFR) AF: 0.262 AC: 10854 AN: 41472

American (AMR) AF: 0.441 AC: 6738 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3472

East Asian (EAS) AF: 0.581 AC: 3009 AN: 5178

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4814

European-Finnish (FIN) AF: 0.590 AC: 6239 AN: 10578

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.468 AC: 31780 AN: 67972

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.420 Hom.: 5417

Bravo AF: 0.398

Asia WGS AF: 0.376 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.92
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs732245; hg19: chr4-15937085; COSMIC: COSV52586255;