4-16016701-C-T

Position:

• chr4-16016701-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006017.3(PROM1):​c.1003-461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,184 control chromosomes in the GnomAD database, including 60,917 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 0.89 (60917 hom., cov: 32)
• Consequence: PROM1 NM_006017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROM1	NM_006017.3	c.1003-461G>A		intron_variant		ENST00000447510.7	NP_006008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7	c.1003-461G>A		intron_variant		1	NM_006017.3	ENSP00000415481	P3

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135672 AN: 152066 Hom.: 60856 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.892 AC: 135792 AN: 152184 Hom.: 60917 Cov.: 32 AF XY: 0.887 AC XY: 65956 AN XY: 74394

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.900

Alfa AF: 0.923 Hom.: 29509

Bravo AF: 0.884

Asia WGS AF: 0.753 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.46

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: rs2531154; hg19: chr4-16018324;