chr4-15936769-C-T

Variant names:

• chr4-15936769-C-T
• rs16892645
• NM_005130.5:c.-20-117G>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.-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
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP1	NM_005130.5	MANE Select	c.-20-117G>A		intron	N/A	NP_005121.1	Q14512

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP1	ENST00000382333.2	TSL:3 MANE Select	c.-20-117G>A		intron	N/A	ENSP00000371770.1	Q14512
	FGFBP1	ENST00000888688.1		c.-20-117G>A		intron	N/A	ENSP00000558747.1
	FGFBP1	ENST00000888689.1		c.-20-117G>A		intron	N/A	ENSP00000558748.1

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

African (AFR) AF: 0.0256 AC: 332 AN: 12958

American (AMR) AF: 0.187 AC: 3406 AN: 18238

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1562 AN: 13816

East Asian (EAS) AF: 0.163 AC: 5091 AN: 31148

South Asian (SAS) AF: 0.146 AC: 6346 AN: 43434

European-Finnish (FIN) AF: 0.0576 AC: 1708 AN: 29664

Middle Eastern (MID) AF: 0.140 AC: 281 AN: 2014

European-Non Finnish (NFE) AF: 0.0920 AC: 27107 AN: 294518

Other (OTH) AF: 0.110 AC: 2947 AN: 26694

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

African (AFR) AF: 0.0267 AC: 1109 AN: 41550

American (AMR) AF: 0.182 AC: 2785 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3470

East Asian (EAS) AF: 0.187 AC: 961 AN: 5152

South Asian (SAS) AF: 0.153 AC: 739 AN: 4816

European-Finnish (FIN) AF: 0.0573 AC: 608 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6396 AN: 67994

Other (OTH) AF: 0.0958 AC: 202 AN: 2108

Alfa AF: 0.0941 Hom.: 2161

Bravo AF: 0.0911

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-1.1
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: rs16892645; hg19: chr4-15938392; COSMIC: COSV52586360;