rs12089523

Positions:

• chr1-214030356-G-A

Variant summary

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

The ENST00000366958.9(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 ENST00000366958.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.2029-5293G>A		intron_variant		ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.2029-5293G>A		intron_variant		1	NM_001270616.2	ENSP00000355925	P1
PROX1	ENST00000435016.2	c.2029-5293G>A		intron_variant		1		ENSP00000400694	P1
	ENST00000607258.2	n.546C>T		non_coding_transcript_exon_variant	1/1

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0950

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.00924

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.00520

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0338 Hom.: 36

Bravo AF: 0.0426

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs12089523; hg19: chr1-214203699;