chr4-16035729-C-T

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.303+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,609,956 control chromosomes in the GnomAD database, including 217,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14768 hom., cov: 33)

Exomes 𝑓: 0.52 ( 202539 hom. )

Consequence

PROM1
NM_006017.3 splice_region, intron

Scores

Splicing: ADA: 0.0001957

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.700

Publications

18 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):

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

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=-0.73).

BP6

Variant 4-16035729-C-T is Benign according to our data. Variant chr4-16035729-C-T is described in ClinVar as Benign. ClinVar VariationId is 259906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 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
PROM1	NM_006017.3	MANE Select	c.303+6G>A	splice_region intron	N/A	NP_006008.1
PROM1	NM_001145847.2		c.277-2220G>A	intron	N/A	NP_001139319.1
PROM1	NM_001145848.2		c.277-2220G>A	intron	N/A	NP_001139320.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PROM1	ENST00000447510.7	TSL:1 MANE Select	c.303+6G>A	splice_region intron	N/A	ENSP00000415481.2
PROM1	ENST00000505450.5	TSL:1	c.277-2220G>A	intron	N/A	ENSP00000426090.1
PROM1	ENST00000508167.5	TSL:1	c.277-2220G>A	intron	N/A	ENSP00000427346.1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60374

AN:

151998

Hom.:

14761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.449

AC:

111659

AN:

248760

AF XY:

0.463

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.517

AC:

753858

AN:

1457840

Hom.:

202539

Cov.:

AF XY:

0.518

AC XY:

375526

AN XY:

725406

show subpopulations

African (AFR)

AF:

0.112

AC:

3745

AN:

33442

American (AMR)

AF:

0.324

AC:

14456

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

13420

AN:

26110

East Asian (EAS)

AF:

0.184

AC:

7312

AN:

39672

South Asian (SAS)

AF:

0.464

AC:

39928

AN:

86098

European-Finnish (FIN)

AF:

0.522

AC:

27794

AN:

53284

Middle Eastern (MID)

AF:

0.520

AC:

2999

AN:

5764

European-Non Finnish (NFE)

AF:

0.555

AC:

615113

AN:

1108540

Other (OTH)

AF:

0.483

AC:

29091

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

17582

35163

52745

70326

87908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16846

33692

50538

67384

84230

<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:

0.397

AC:

60376

AN:

152116

Hom.:

14768

Cov.:

AF XY:

0.394

AC XY:

29328

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.121

AC:

5044

AN:

41520

American (AMR)

AF:

0.392

AC:

5983

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1758

AN:

3466

East Asian (EAS)

AF:

0.158

AC:

819

AN:

5176

South Asian (SAS)

AF:

0.447

AC:

2156

AN:

4826

European-Finnish (FIN)

AF:

0.516

AC:

5457

AN:

10572

Middle Eastern (MID)

AF:

0.548

AC:

159

AN:

290

European-Non Finnish (NFE)

AF:

0.551

AC:

37465

AN:

67976

Other (OTH)

AF:

0.455

AC:

960

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1619

3239

4858

6478

8097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.492

Hom.:

61180

Bravo

AF:

0.375

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

EpiCase

AF:

0.565

EpiControl

AF:

0.559

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Cone-rod dystrophy 12 (2)

Retinal macular dystrophy type 2 (2)

Stargardt disease 4 (2)

Retinitis pigmentosa (1)

Retinitis pigmentosa 41 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.2

(source)

DANN

Benign

0.59

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.090

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