4-15936108-T-C

Position:

• chr4-15936108-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005130.5(FGFBP1):​c.525A>G​(p.Lys175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,614,062 control chromosomes in the GnomAD database, including 745,692 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 0.94 (67820 hom., cov: 30)
  • Exomes 𝑓: 0.96 (677872 hom.)
• Consequence: FGFBP1 NM_005130.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFBP1	NM_005130.5	c.525A>G	p.Lys175=	synonymous_variant	3/3	ENST00000382333.2	NP_005121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFBP1	ENST00000382333.2	c.525A>G	p.Lys175=	synonymous_variant	3/3	3	NM_005130.5	ENSP00000371770	P1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143438 AN: 152082 Hom.: 67783 Cov.: 30

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.950

GnomAD3 exomes AF: 0.956 AC: 240300 AN: 251396 Hom.: 115100 AF XY: 0.958 AC XY: 130118 AN XY: 135860

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.982

Gnomad ASJ exome AF: 0.977

Gnomad EAS exome AF: 0.823

Gnomad SAS exome AF: 0.976

Gnomad FIN exome AF: 0.986

Gnomad NFE exome AF: 0.964

Gnomad OTH exome AF: 0.964

GnomAD4 exome AF: 0.963 AC: 1407337 AN: 1461862 Hom.: 677872 Cov.: 59 AF XY: 0.963 AC XY: 700615 AN XY: 727238

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.976

Gnomad4 EAS exome AF: 0.863

Gnomad4 SAS exome AF: 0.975

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.966

Gnomad4 OTH exome AF: 0.954

GnomAD4 genome AF: 0.943 AC: 143528 AN: 152200 Hom.: 67820 Cov.: 30 AF XY: 0.944 AC XY: 70281 AN XY: 74416

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.947

Alfa AF: 0.960 Hom.: 133169

Bravo AF: 0.939

Asia WGS AF: 0.879 AC: 3058 AN: 3478

EpiCase AF: 0.963

EpiControl AF: 0.963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.64

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: rs2072313; hg19: chr4-15937731;