1-213987186-G-A

Variant names:

• chr1-213987186-G-A
• rs340873
• ENST00000471129.1:c.-68+3863G>A

Variant summary

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

The ENST00000471129.1(PROX1):​c.-68+3863G>A variant causes a intron 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 ENST00000471129.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 8 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471129.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000471129.1	TSL:3	c.-68+3863G>A		intron	N/A	ENSP00000419517.1
	PROX1-AS1	ENST00000433082.6	TSL:5	n.62+1135C>T		intron	N/A
	PROX1-AS1	ENST00000598091.1	TSL:5	n.51+394C>T		intron	N/A

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

African (AFR) AF: 0.284 AC: 11787 AN: 41462

American (AMR) AF: 0.505 AC: 7706 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3468

East Asian (EAS) AF: 0.572 AC: 2949 AN: 5160

South Asian (SAS) AF: 0.591 AC: 2844 AN: 4812

European-Finnish (FIN) AF: 0.452 AC: 4781 AN: 10578

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36974 AN: 67962

Other (OTH) AF: 0.459 AC: 969 AN: 2110

Alfa AF: 0.515 Hom.: 26152

Bravo AF: 0.458

Asia WGS AF: 0.549 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		0.039

Splicing

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

Other links and lift over

dbSNP: rs340873; hg19: chr1-214160529;