rs340873

Positions:

• chr1-213987186-G-A
• chr1-213987186-G-T

Variant summary

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

The ENST00000433082.6(PROX1-AS1):​n.62+1135C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,030 control chromosomes in the GnomAD database, including 17,306 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 0.46 (17306 hom., cov: 32)
• Consequence: PROX1-AS1 ENST00000433082.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	XM_011509773.3	c.-68+3863G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1-AS1	ENST00000433082.6	n.62+1135C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70428 AN: 151910 Hom.: 17305 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70447 AN: 152030 Hom.: 17306 Cov.: 32 AF XY: 0.461 AC XY: 34218 AN XY: 74306

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.459

Alfa AF: 0.525 Hom.: 20521

Bravo AF: 0.458

Asia WGS AF: 0.549 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs340873; hg19: chr1-214160529;