4-15991208-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000447510.7(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
ENST00000447510.7 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0260
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15991208-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PROM1NM_006017.3 linkuse as main transcriptc.1983+14G>A intron_variant ENST00000447510.7 NP_006008.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PROM1ENST00000447510.7 linkuse as main transcriptc.1983+14G>A intron_variant 1 NM_006017.3 ENSP00000415481 P3O43490-1

Frequencies

GnomAD3 genomes
AF:
0.0453
AC:
6889
AN:
152140
Hom.:
318
Cov.:
32
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
GnomAD3 exomes
AF:
0.0486
AC:
11577
AN:
238268
Hom.:
624
AF XY:
0.0452
AC XY:
5856
AN XY:
129532
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 SAS exome
AF:
0.0696
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.:
29
AF XY:
0.0256
AC XY:
18377
AN XY:
718176
show subpopulations
Gnomad4 AFR exome
AF:
0.0768
Gnomad4 AMR exome
AF:
0.102
Gnomad4 ASJ exome
AF:
0.0241
Gnomad4 EAS exome
AF:
0.180
Gnomad4 SAS exome
AF:
0.0669
Gnomad4 FIN exome
AF:
0.0300
Gnomad4 NFE exome
AF:
0.0115
Gnomad4 OTH exome
AF:
0.0317
GnomAD4 genome
AF:
0.0453
AC:
6901
AN:
152258
Hom.:
319
Cov.:
32
AF XY:
0.0475
AC XY:
3539
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0772
Gnomad4 AMR
AF:
0.0624
Gnomad4 ASJ
AF:
0.0219
Gnomad4 EAS
AF:
0.190
Gnomad4 SAS
AF:
0.0910
Gnomad4 FIN
AF:
0.0309
Gnomad4 NFE
AF:
0.0121
Gnomad4 OTH
AF:
0.0350
Alfa
AF:
0.0365
Hom.:
43
Bravo
AF:
0.0505
Asia WGS
AF:
0.118
AC:
409
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Stargardt disease 4 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Retinal macular dystrophy type 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Cone-rod dystrophy 12 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Retinitis pigmentosa Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.0
DANN
Benign
0.56

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.

Other links and lift over

dbSNP: rs4698436; hg19: chr4-15992831; API