4-15936108-T-C

Variant names:

• chr4-15936108-T-C
• rs2072313
• NM_005130.5:c.525A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005130.5(FGFBP1):​c.525A>G​(p.Lys175Lys) 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
• Publications: 17 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 -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 rank	MANE	Protein	UniProt
FGFBP1	NM_005130.5	c.525A>G	p.Lys175Lys	synonymous_variant	Exon 3 of 3	ENST00000382333.2	NP_005121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFBP1	ENST00000382333.2	c.525A>G	p.Lys175Lys	synonymous_variant	Exon 3 of 3	3	NM_005130.5	ENSP00000371770.1

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

GnomAD2 exomes AF: 0.956 AC: 240300 AN: 251396 AF XY: 0.958

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 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

African (AFR) AF: 0.894 AC: 29943 AN: 33480

American (AMR) AF: 0.980 AC: 43817 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 25507 AN: 26136

East Asian (EAS) AF: 0.863 AC: 34264 AN: 39696

South Asian (SAS) AF: 0.975 AC: 84128 AN: 86256

European-Finnish (FIN) AF: 0.985 AC: 52595 AN: 53420

Middle Eastern (MID) AF: 0.974 AC: 5617 AN: 5766

European-Non Finnish (NFE) AF: 0.966 AC: 1073850 AN: 1111990

Other (OTH) AF: 0.954 AC: 57616 AN: 60396

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

African (AFR) AF: 0.898 AC: 37230 AN: 41480

American (AMR) AF: 0.961 AC: 14709 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3394 AN: 3472

East Asian (EAS) AF: 0.824 AC: 4257 AN: 5166

South Asian (SAS) AF: 0.972 AC: 4691 AN: 4824

European-Finnish (FIN) AF: 0.987 AC: 10465 AN: 10604

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65585 AN: 68028

Other (OTH) AF: 0.947 AC: 2001 AN: 2112

Alfa AF: 0.957 Hom.: 191541

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
PhyloP100		-1.4
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: rs2072313; hg19: chr4-15937731; COSMIC: COSV108063854;