Variant NM_006017.3:c.2374-4dupC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006017.3(PROM1):c.2374-4dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,485,620 control chromosomes in the GnomAD database, including 51,835 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6655 hom., cov: 0)

Exomes 𝑓: 0.26 ( 45180 hom. )

Consequence

PROM1
NM_006017.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.539

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-15980540-A-AG is Benign according to our data. Variant chr4-15980540-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 95333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROM1	NM_006017.3 link	c.2374-4dupC		splice_region_variant, intron_variant	Intron 23 of 27	ENST00000447510.7	NP_006008.1	O43490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7 link	c.2374-4_2374-3insC		splice_region_variant, intron_variant	Intron 23 of 27	1	NM_006017.3	ENSP00000415481.2		O43490-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44022

AN:

150920

Hom.:

6657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.359

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.282

AC:

41237

AN:

146440

Hom.:

5795

AF XY:

0.278

AC XY:

21518

AN XY:

77404

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.256

AC:

341110

AN:

1334584

Hom.:

45180

Cov.:

AF XY:

0.256

AC XY:

169101

AN XY:

660612

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.292

AC:

44029

AN:

151036

Hom.:

6655

Cov.:

AF XY:

0.294

AC XY:

21696

AN XY:

73748

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.262

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.235

Hom.:

922

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 14, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stargardt Disease, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macular dystrophy, retinal

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-Rod Dystrophy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over