rs17478107

Variant names:

• chr4-16000665-T-C
• rs17478107
• NM_006017.3:c.1455-46A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-16000665-T-C
• chr4-16000665-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.715
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROM1	NM_006017.3	MANE Select	c.1455-46A>G		intron	N/A	NP_006008.1	O43490-1
	PROM1	NM_001145847.2		c.1428-46A>G		intron	N/A	NP_001139319.1	O43490-2
	PROM1	NM_001145848.2		c.1428-46A>G		intron	N/A	NP_001139320.1	O43490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROM1	ENST00000447510.7	TSL:1 MANE Select	c.1455-46A>G		intron	N/A	ENSP00000415481.2	O43490-1
	PROM1	ENST00000505450.5	TSL:1	c.1428-46A>G		intron	N/A	ENSP00000426090.1	O43490-2
	PROM1	ENST00000508167.5	TSL:1	c.1428-46A>G		intron	N/A	ENSP00000427346.1	O43490-2

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

GnomAD2 exomes AF: 0.276 AC: 49024 AN: 177716 AF XY: 0.283

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 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

African (AFR) AF: 0.0496 AC: 1462 AN: 29458

American (AMR) AF: 0.261 AC: 9442 AN: 36220

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 6259 AN: 22796

East Asian (EAS) AF: 0.161 AC: 6107 AN: 37946

South Asian (SAS) AF: 0.323 AC: 23609 AN: 73016

European-Finnish (FIN) AF: 0.345 AC: 15733 AN: 45656

Middle Eastern (MID) AF: 0.270 AC: 1441 AN: 5328

European-Non Finnish (NFE) AF: 0.303 AC: 299559 AN: 989022

Other (OTH) AF: 0.275 AC: 14894 AN: 54160

GnomAD4 genome AF: 0.226 AC: 34436 AN: 152170 Hom.: 4710 Cov.: 32 AF XY: 0.228 AC XY: 16934 AN XY: 74390

African (AFR) AF: 0.0623 AC: 2588 AN: 41530

American (AMR) AF: 0.232 AC: 3544 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.136 AC: 704 AN: 5182

South Asian (SAS) AF: 0.308 AC: 1486 AN: 4824

European-Finnish (FIN) AF: 0.338 AC: 3577 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20649 AN: 67982

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.256 Hom.: 6624

Bravo AF: 0.213

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.68
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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