Variant 4-16000665-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006017.3(PROM1):c.1455-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,445,772 control chromosomes in the GnomAD database, including 61,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4710 hom., cov: 32)

Exomes 𝑓: 0.29 ( 56779 hom. )

Consequence

PROM1
NM_006017.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.715

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:

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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=-0.84).

BP6

Variant 4-16000665-T-C is Benign according to our data. Variant chr4-16000665-T-C is described in ClinVar as [Benign]. Clinvar id is 1245372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROM1	NM_006017.3 linkuse as main transcript	c.1455-46A>G		intron_variant		ENST00000447510.7	NP_006008.1	O43490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7 linkuse as main transcript	c.1455-46A>G		intron_variant		1	NM_006017.3	ENSP00000415481.2		O43490-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34413

AN:

152052

Hom.:

4705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.276

AC:

49024

AN:

177716

Hom.:

7161

AF XY:

0.283

AC XY:

26953

AN XY:

95222

show subpopulations

Gnomad AFR exome

AF:

0.0537

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.293

AC:

378506

AN:

1293602

Hom.:

56779

Cov.:

AF XY:

0.294

AC XY:

188387

AN XY:

641404

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.323

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.226

AC:

34436

AN:

152170

Hom.:

4710

Cov.:

AF XY:

0.228

AC XY:

16934

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0623

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.284

Hom.:

4607

Bravo

AF:

0.213

Asia WGS

AF:

0.194

AC:

676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.32

DANN

Benign

0.68

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