rs340839

Positions:

• chr1-213988477-G-A
• chr1-213988477-G-C
• chr1-213988477-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000366958.9(PROX1):​c.-74G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.416 in 150,840 control chromosomes in the GnomAD database, including 13,761 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 0.42 (13739 hom., cov: 28)
  • Exomes 𝑓: 0.44 (22 hom.)
• Consequence: PROX1 ENST00000366958.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30

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]

PROX1-AS1 (HGNC:43656): (PROX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.-74G>A		5_prime_UTR_variant	1/5	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.-74G>A		5_prime_UTR_variant	1/5	1	NM_001270616.2	ENSP00000355925	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62676 AN: 150492 Hom.: 13742 Cov.: 28

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.442 AC: 106 AN: 240 Hom.: 22 Cov.: 0 AF XY: 0.426 AC XY: 75 AN XY: 176

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.416 AC: 62682 AN: 150600 Hom.: 13739 Cov.: 28 AF XY: 0.413 AC XY: 30357 AN XY: 73478

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.428

Alfa AF: 0.471 Hom.: 28333

Bravo AF: 0.413

Asia WGS AF: 0.510 AC: 1772 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs340839; hg19: chr1-214161820;