NM_006017.3:c.221-6835A>T

Variant names:

• chr4-16045836-T-A
• rs7680363
• NM_006017.3:c.221-6835A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006017.3(PROM1):​c.221-6835A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,128 control chromosomes in the GnomAD database, including 1,190 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1190 hom., cov: 32)
• Consequence: PROM1 NM_006017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 3 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):

• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROM1	NM_006017.3	c.221-6835A>T		intron_variant	Intron 2 of 27	ENST00000447510.7	NP_006008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7	c.221-6835A>T		intron_variant	Intron 2 of 27	1	NM_006017.3	ENSP00000415481.2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17291 AN: 152010 Hom.: 1189 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17310 AN: 152128 Hom.: 1190 Cov.: 32 AF XY: 0.122 AC XY: 9061 AN XY: 74382

African (AFR) AF: 0.133 AC: 5527 AN: 41478

American (AMR) AF: 0.166 AC: 2536 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1191 AN: 5170

South Asian (SAS) AF: 0.166 AC: 799 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1708 AN: 10598

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0684 AC: 4649 AN: 67994

Other (OTH) AF: 0.107 AC: 227 AN: 2114

Alfa AF: 0.0934 Hom.: 106

Bravo AF: 0.113

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		0.15
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: rs7680363; hg19: chr4-16047459;