4-15968578-G-C

Variant names:

• chr4-15968578-G-C
• rs7686732
• ENST00000513448.5:n.1694C>G

Variant summary

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

The ENST00000513448.5(PROM1):​n.1694C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,256 control chromosomes in the GnomAD database, including 56,807 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 0.86 (56807 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PROM1 ENST00000513448.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROM1	NM_006017.3	c.*815C>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000447510.7	NP_006008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7	c.*815C>G		3_prime_UTR_variant	Exon 28 of 28	1	NM_006017.3	ENSP00000415481.2

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130750 AN: 152138 Hom.: 56774 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.851

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.859 AC: 130845 AN: 152256 Hom.: 56807 Cov.: 33 AF XY: 0.865 AC XY: 64388 AN XY: 74458

African (AFR) AF: 0.725 AC: 30098 AN: 41500

American (AMR) AF: 0.899 AC: 13761 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5188

South Asian (SAS) AF: 0.953 AC: 4607 AN: 4834

European-Finnish (FIN) AF: 0.931 AC: 9879 AN: 10614

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61398 AN: 68030

Other (OTH) AF: 0.851 AC: 1798 AN: 2112

Alfa AF: 0.883 Hom.: 3455

Bravo AF: 0.849

Asia WGS AF: 0.966 AC: 3357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7686732; hg19: chr4-15970201;