rs2531174

Positions:

• chr4-15938582-G-A
• chr4-15938582-G-C
• chr4-15938582-G-T

Variant summary

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

The NM_005130.5(FGFBP1):​c.-242+105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,468 control chromosomes in the GnomAD database, including 68,911 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 0.95 (68801 hom., cov: 31)
  • Exomes 𝑓: 0.97 (110 hom.)
• Consequence: FGFBP1 NM_005130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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=-0.85).
• 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.-242+105C>T		intron_variant		ENST00000382333.2	NP_005121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFBP1	ENST00000382333.2	c.-242+105C>T		intron_variant		3	NM_005130.5	ENSP00000371770.1

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144525 AN: 152118 Hom.: 68755 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.954

GnomAD4 exome AF: 0.974 AC: 226 AN: 232 Hom.: 110 Cov.: 0 AF XY: 0.984 AC XY: 124 AN XY: 126

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.988

Gnomad4 NFE exome AF: 0.957

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.950 AC: 144627 AN: 152236 Hom.: 68801 Cov.: 31 AF XY: 0.951 AC XY: 70783 AN XY: 74430

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.952

Alfa AF: 0.963 Hom.: 31855

Bravo AF: 0.947

Asia WGS AF: 0.878 AC: 3053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.52
DANN	Benign	0.28

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: rs2531174; hg19: chr4-15940205;