4-15963077-A-G

Variant names:

• chr4-15963077-A-G
• NM_031950.4:c.53T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031950.4(FGFBP2):​c.53T>C​(p.Leu18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGFBP2 NM_031950.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.742
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24243614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031950.4. 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.53T>C	p.Leu18Ser	missense	Exon 1 of 2	NP_114156.1	Q9BYJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP2	ENST00000259989.7	TSL:1 MANE Select	c.53T>C	p.Leu18Ser	missense	Exon 1 of 2	ENSP00000259989.6	Q9BYJ0
	FGFBP2	ENST00000899354.1		c.53T>C	p.Leu18Ser	missense	Exon 2 of 3	ENSP00000569413.1
	PROM1	ENST00000503884.5	TSL:3	n.*424T>C		splice_region non_coding_transcript_exon	Exon 7 of 7	ENSP00000423860.1	H0Y9D4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.74
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.61		Gain of catalytic residue at L18 (P = 0.003)
MVP		0.19
MPC		0.31
ClinPred		0.32	T
GERP RS		-2.6
PromoterAI		0.0083	Neutral
Varity_R		0.090
gMVP		0.39
Mutation Taster		=94/6	polymorphism

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

hg19: chr4-15964700;