rs2058147

Variant names:

• chr4-15990863-C-T
• rs2058147
• NM_006017.3:c.1983+359G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006017.3. 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
	PROM1	NM_006017.3	MANE Select	c.1983+359G>A		intron	N/A	NP_006008.1	O43490-1
	PROM1	NM_001145847.2		c.1956+359G>A		intron	N/A	NP_001139319.1	O43490-2
	PROM1	NM_001145848.2		c.1956+359G>A		intron	N/A	NP_001139320.1	O43490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROM1	ENST00000447510.7	TSL:1 MANE Select	c.1983+359G>A		intron	N/A	ENSP00000415481.2	O43490-1
	PROM1	ENST00000505450.5	TSL:1	c.1956+359G>A		intron	N/A	ENSP00000426090.1	O43490-2
	PROM1	ENST00000508167.5	TSL:1	c.1956+359G>A		intron	N/A	ENSP00000427346.1	O43490-2

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

African (AFR) AF: 0.937 AC: 38946 AN: 41578

American (AMR) AF: 0.940 AC: 14391 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4397 AN: 5178

South Asian (SAS) AF: 0.896 AC: 4333 AN: 4834

European-Finnish (FIN) AF: 0.909 AC: 9651 AN: 10618

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66162 AN: 68044

Other (OTH) AF: 0.946 AC: 2001 AN: 2116

Alfa AF: 0.964 Hom.: 265758

Bravo AF: 0.951

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2058147; hg19: chr4-15992486;