4-16000665-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.715

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
PROM1	NM_006017.3	c.1455-46A>G		intron_variant		ENST00000447510.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROM1	ENST00000447510.7	c.1455-46A>G		intron_variant		1	NM_006017.3	P3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34413 AN: 152052 Hom.: 4705 Cov.: 32

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

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.: 20 AF XY: 0.294 AC XY: 188387 AN XY: 641404

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.: 32 AF XY: 0.228 AC XY: 16934 AN XY: 74390

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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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

Other links and lift over

dbSNP: rs17478107; hg19: chr4-16002288; COSMIC: COSV71699611; COSMIC: COSV71699611;