4-15963240-G-T

Variant names:

• chr4-15963240-G-T
• rs4698433
• ENST00000899354.1:c.-31+42C>A

Variant summary

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

The ENST00000899354.1(FGFBP2):​c.-31+42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,140,408 control chromosomes in the GnomAD database, including 80,783 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 0.33 (9386 hom., cov: 33)
  • Exomes 𝑓: 0.37 (71397 hom.)
• Consequence: FGFBP2 ENST00000899354.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 16 publications found

Genes affected

FGFBP2 (HGNC:29451): (fibroblast growth factor binding protein 2) This gene encodes a member of the fibroblast growth factor binding protein family. The encoded protein is a serum protein that is selectively secreted by cytotoxic lymphocytes and may be involved in cytotoxic lymphocyte-mediated immunity. An increase in the amount of gene product may be associated with atopic asthma and mild extrinsic asthma.[provided by RefSeq Staff, Oct 2008]

PROM1 (HGNC:9454): (prominin 1) This gene encodes a pentaspan transmembrane glycoprotein. The protein localizes to membrane protrusions and is often expressed on adult stem cells, where it is thought to function in maintaining stem cell properties by suppressing differentiation. Mutations in this gene have been shown to result in retinitis pigmentosa and Stargardt disease. Expression of this gene is also associated with several types of cancer. This gene is expressed from at least five alternative promoters that are expressed in a tissue-dependent manner. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

PROM1 Gene-Disease associations (from GenCC):

• PROM1-related dominant retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinal macular dystrophy type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• PROM1-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 41

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cone-rod dystrophy 12

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Stargardt disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000899354.1. 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
	FGFBP2	NM_031950.4	MANE Select	c.-111C>A		upstream_gene	N/A	NP_114156.1	Q9BYJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP2	ENST00000899354.1		c.-31+42C>A		intron	N/A	ENSP00000569413.1
	PROM1	ENST00000503884.5	TSL:3	n.*342-81C>A		intron	N/A	ENSP00000423860.1	H0Y9D4
	FGFBP2	ENST00000509331.1	TSL:2	n.83-2629C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50630 AN: 152020 Hom.: 9377 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.372 AC: 367665 AN: 988270 Hom.: 71397 Cov.: 13 AF XY: 0.378 AC XY: 186078 AN XY: 492534

African (AFR) AF: 0.160 AC: 3751 AN: 23468

American (AMR) AF: 0.550 AC: 13304 AN: 24210

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 8140 AN: 16680

East Asian (EAS) AF: 0.273 AC: 9930 AN: 36392

South Asian (SAS) AF: 0.530 AC: 30073 AN: 56694

European-Finnish (FIN) AF: 0.351 AC: 15975 AN: 45572

Middle Eastern (MID) AF: 0.391 AC: 1171 AN: 2994

European-Non Finnish (NFE) AF: 0.364 AC: 269247 AN: 738966

Other (OTH) AF: 0.371 AC: 16074 AN: 43294

GnomAD4 genome AF: 0.333 AC: 50659 AN: 152138 Hom.: 9386 Cov.: 33 AF XY: 0.339 AC XY: 25192 AN XY: 74338

African (AFR) AF: 0.176 AC: 7293 AN: 41528

American (AMR) AF: 0.489 AC: 7477 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5172

South Asian (SAS) AF: 0.544 AC: 2620 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3570 AN: 10554

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25322 AN: 67994

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.351 Hom.: 4956

Bravo AF: 0.338

Asia WGS AF: 0.399 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.73
PhyloP100		0.49
PromoterAI		-0.20	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4698433; hg19: chr4-15964863; COSMIC: COSV52588772;