4-15963240-G-T

Variant summary

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

The ENST00000503884.5(PROM1):c.*342-81C>A variant causes a intron, NMD transcript 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: PROM1 ENST00000503884.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROM1	ENST00000503884.5	c.*342-81C>A		intron_variant, NMD_transcript_variant		3
FGFBP2	ENST00000509331.1	n.83-2629C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.371

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

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.370

Alfa AF: 0.350 Hom.: 4412

Bravo AF: 0.338

Asia WGS AF: 0.399 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.3
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

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