4-15993691-C-T

Position:

• chr4-15993691-C-T

Variant summary

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

The NM_006017.3(PROM1):​c.1767+296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,002 control chromosomes in the GnomAD database, including 14,074 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 0.43 (14074 hom., cov: 32)
• Consequence: PROM1 NM_006017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROM1	NM_006017.3	c.1767+296G>A		intron_variant		ENST00000447510.7	NP_006008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7	c.1767+296G>A		intron_variant		1	NM_006017.3	ENSP00000415481.2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64763 AN: 151884 Hom.: 14077 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64769 AN: 152002 Hom.: 14074 Cov.: 32 AF XY: 0.428 AC XY: 31812 AN XY: 74298

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.453

Alfa AF: 0.461 Hom.: 21279

Bravo AF: 0.426

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.49

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: rs717176; hg19: chr4-15995314;