4-15993502-A-G

Variant names:

• chr4-15993502-A-G
• rs17387100
• NM_006017.3:c.1767+485T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006017.3(PROM1):​c.1767+485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,250 control chromosomes in the GnomAD database, including 462 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 0.073 (462 hom., cov: 32)
• Consequence: PROM1 NM_006017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 10 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):

• retinal macular dystrophy type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• inherited retinal dystrophy

  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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROM1	NM_006017.3	MANE Select	c.1767+485T>C		intron	N/A	NP_006008.1
	PROM1	NM_001145847.2		c.1740+485T>C		intron	N/A	NP_001139319.1
	PROM1	NM_001145848.2		c.1740+485T>C		intron	N/A	NP_001139320.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROM1	ENST00000447510.7	TSL:1 MANE Select	c.1767+485T>C		intron	N/A	ENSP00000415481.2
	PROM1	ENST00000505450.5	TSL:1	c.1740+485T>C		intron	N/A	ENSP00000426090.1
	PROM1	ENST00000508167.5	TSL:1	c.1740+485T>C		intron	N/A	ENSP00000427346.1

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11177 AN: 152132 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0734 AC: 11174 AN: 152250 Hom.: 462 Cov.: 32 AF XY: 0.0703 AC XY: 5229 AN XY: 74430

African (AFR) AF: 0.0894 AC: 3712 AN: 41530

American (AMR) AF: 0.0580 AC: 887 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4824

European-Finnish (FIN) AF: 0.0625 AC: 663 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0770 AC: 5236 AN: 68016

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0771 Hom.: 1115

Bravo AF: 0.0753

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.69
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: rs17387100; hg19: chr4-15995125;