rs12089523

Variant names:

• chr1-214030356-G-A
• rs12089523
• NM_001270616.2:c.2029-5293G>A

Variant summary

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

The NM_001270616.2(PROX1):​c.2029-5293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,102 control chromosomes in the GnomAD database, including 229 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 0.042 (229 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 4 publications found

Genes affected

PROX1 (HGNC:9459): (prospero homeobox 1) The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ENSG00000272167 (HGNC:):

LINC02775 (HGNC:54294): (long intergenic non-protein coding RNA 2775)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270616.2. 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
	PROX1	NM_001270616.2	MANE Select	c.2029-5293G>A		intron	N/A	NP_001257545.1	Q92786
	PROX1	NM_002763.5		c.2029-5293G>A		intron	N/A	NP_002754.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.2029-5293G>A		intron	N/A	ENSP00000355925.4	Q92786
	PROX1	ENST00000435016.2	TSL:1	c.2029-5293G>A		intron	N/A	ENSP00000400694.1	Q92786
	PROX1	ENST00000881021.1		c.2029-5290G>A		intron	N/A	ENSP00000551080.1

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6362 AN: 151984 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0354

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

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: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0420 AC: 6393 AN: 152102 Hom.: 229 Cov.: 32 AF XY: 0.0418 AC XY: 3110 AN XY: 74336

African (AFR) AF: 0.0950 AC: 3939 AN: 41478

American (AMR) AF: 0.0219 AC: 334 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00924 AC: 32 AN: 3464

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5166

South Asian (SAS) AF: 0.00520 AC: 25 AN: 4810

European-Finnish (FIN) AF: 0.0496 AC: 525 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1365 AN: 67998

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0472 Hom.: 121

Bravo AF: 0.0426

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.025
DANN	Benign	0.43
PhyloP100		-0.30
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12089523;

hg19: chr1-214203699;