NM_006017.3:c.1983+14G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006017.3(PROM1):c.1983+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,595,646 control chromosomes in the GnomAD database, including 1,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 319 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1441 hom. )

Consequence

PROM1
NM_006017.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0260

Publications

9 publications found

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 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

PROM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-15991208-C-T is Benign according to our data. Variant chr4-15991208-C-T is described in ClinVar as Benign. ClinVar VariationId is 259905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PROM1	NM_006017.3	MANE Select	c.1983+14G>A	intron	N/A	NP_006008.1	O43490-1
PROM1	NM_001145847.2		c.1956+14G>A	intron	N/A	NP_001139319.1	O43490-2
PROM1	NM_001145848.2		c.1956+14G>A	intron	N/A	NP_001139320.1	O43490-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PROM1	ENST00000447510.7	TSL:1 MANE Select	c.1983+14G>A	intron	N/A	ENSP00000415481.2	O43490-1
PROM1	ENST00000505450.5	TSL:1	c.1956+14G>A	intron	N/A	ENSP00000426090.1	O43490-2
PROM1	ENST00000508167.5	TSL:1	c.1956+14G>A	intron	N/A	ENSP00000427346.1	O43490-2

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6889

AN:

152140

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.0913

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0486

AC:

11577

AN:

238268

AF XY:

0.0452

show subpopulations

Gnomad AFR exome

AF:

0.0747

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0330

GnomAD4 exome

AF:

0.0251

AC:

36170

AN:

1443388

Hom.:

1441

Cov.:

AF XY:

0.0256

AC XY:

18377

AN XY:

718176

show subpopulations

African (AFR)

AF:

0.0768

AC:

2507

AN:

32650

American (AMR)

AF:

0.102

AC:

4291

AN:

42072

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

625

AN:

25928

East Asian (EAS)

AF:

0.180

AC:

6982

AN:

38790

South Asian (SAS)

AF:

0.0669

AC:

5576

AN:

83352

European-Finnish (FIN)

AF:

0.0300

AC:

1596

AN:

53284

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0115

AC:

12639

AN:

1101792

Other (OTH)

AF:

0.0317

AC:

1894

AN:

59794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

1457

2913

4370

5826

7283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0453

AC:

6901

AN:

152258

Hom.:

319

Cov.:

AF XY:

0.0475

AC XY:

3539

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0772

AC:

3209

AN:

41548

American (AMR)

AF:

0.0624

AC:

955

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3468

East Asian (EAS)

AF:

0.190

AC:

984

AN:

5174

South Asian (SAS)

AF:

0.0910

AC:

439

AN:

4824

European-Finnish (FIN)

AF:

0.0309

AC:

327

AN:

10598

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

825

AN:

68032

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

325

650

976

1301

1626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0365

Hom.:

Bravo

AF:

0.0505

Asia WGS

AF:

0.118

AC:

409

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Cone-rod dystrophy 12 (1)

not specified (1)

Retinal macular dystrophy type 2 (1)

Retinitis pigmentosa (1)

Stargardt disease 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.0

(source)

DANN

Benign

0.56

PhyloP100

-0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over