4-15968250-T-G

Variant names:

• chr4-15968250-T-G
• rs544424652
• NM_006017.3:c.*1143A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006017.3(PROM1):​c.*1143A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PROM1 NM_006017.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 2.88
• Publications: 0 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]

FGFBP2 (HGNC:29451): (fibroblast growth factor binding protein 2) This gene encodes a member of the fibroblast growth factor binding protein family. The encoded protein is a serum protein that is selectively secreted by cytotoxic lymphocytes and may be involved in cytotoxic lymphocyte-mediated immunity. An increase in the amount of gene product may be associated with atopic asthma and mild extrinsic asthma.[provided by RefSeq Staff, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).

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.*1143A>C		3_prime_UTR	Exon 28 of 28	NP_006008.1	O43490-1
	PROM1	NM_001145847.2		c.*1143A>C		3_prime_UTR	Exon 27 of 27	NP_001139319.1	O43490-2
	PROM1	NM_001145848.2		c.*1143A>C		3_prime_UTR	Exon 27 of 27	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.*1143A>C		3_prime_UTR	Exon 28 of 28	ENSP00000415481.2	O43490-1
	PROM1	ENST00000505450.5	TSL:1	c.*1143A>C		3_prime_UTR	Exon 27 of 27	ENSP00000426090.1	O43490-2
	PROM1	ENST00000508167.5	TSL:1	c.*1143A>C		3_prime_UTR	Exon 27 of 27	ENSP00000427346.1	O43490-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cone-rod dystrophy 12 (1)
-	1	-	Retinal macular dystrophy type 2 (1)
-	1	-	Retinitis pigmentosa (1)
-	1	-	Stargardt disease 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		2.9

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: rs544424652; hg19: chr4-15969873;