rs2058147

Positions:

• chr4-15990863-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.1983+359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,354 control chromosomes in the GnomAD database, including 68,575 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 0.95 (68575 hom., cov: 34)
• Consequence: PROM1 NM_006017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROM1	NM_006017.3	c.1983+359G>A		intron_variant		ENST00000447510.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROM1	ENST00000447510.7	c.1983+359G>A		intron_variant		1	NM_006017.3	P3

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144366 AN: 152236 Hom.: 68543 Cov.: 34

Gnomad AFR AF: 0.937

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.948 AC: 144451 AN: 152354 Hom.: 68575 Cov.: 34 AF XY: 0.944 AC XY: 70350 AN XY: 74498

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.970

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.946

Alfa AF: 0.968 Hom.: 116129

Bravo AF: 0.951

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.31

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: rs2058147; hg19: chr4-15992486;