rs2240688

Variant names:

• chr4-15968726-T-G
• rs2240688
• NM_006017.3:c.*667A>C

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.*667A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,218 control chromosomes in the GnomAD database, including 4,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4370 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: PROM1 NM_006017.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0640
• Publications: 33 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-15968726-T-G is Benign according to our data. Variant chr4-15968726-T-G is described in ClinVar as Benign. ClinVar VariationId is 347968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 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.*667A>C		3_prime_UTR	Exon 28 of 28	NP_006008.1	O43490-1
	PROM1	NM_001145847.2		c.*667A>C		3_prime_UTR	Exon 27 of 27	NP_001139319.1	O43490-2
	PROM1	NM_001145848.2		c.*667A>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.*667A>C		3_prime_UTR	Exon 28 of 28	ENSP00000415481.2	O43490-1
	PROM1	ENST00000505450.5	TSL:1	c.*667A>C		3_prime_UTR	Exon 27 of 27	ENSP00000426090.1	O43490-2
	PROM1	ENST00000508167.5	TSL:1	c.*667A>C		3_prime_UTR	Exon 27 of 27	ENSP00000427346.1	O43490-2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33312 AN: 152098 Hom.: 4372 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.219 AC: 33298 AN: 152216 Hom.: 4370 Cov.: 33 AF XY: 0.225 AC XY: 16776 AN XY: 74414

African (AFR) AF: 0.0699 AC: 2906 AN: 41562

American (AMR) AF: 0.287 AC: 4381 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1064 AN: 4828

European-Finnish (FIN) AF: 0.362 AC: 3833 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17991 AN: 68000

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.243 Hom.: 14577

Bravo AF: 0.204

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.87
CADD	Benign	0.68
DANN	Benign	0.73
PhyloP100		-0.064
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: rs2240688; hg19: chr4-15970349;