chr1-213987205-A-T

Variant names:

• chr1-213987205-A-T
• rs340872
• ENST00000471129.1:c.-68+3882A>T

Variant summary

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

The ENST00000471129.1(PROX1):​c.-68+3882A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,994 control chromosomes in the GnomAD database, including 17,410 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 0.47 (17410 hom., cov: 32)
• Consequence: PROX1 ENST00000471129.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 7 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=-0.89).
• 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 rank	MANE	Protein	UniProt
PROX1	XM_011509773.3	c.-68+3882A>T		intron_variant	Intron 1 of 4		XP_011508075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000471129.1	c.-68+3882A>T		intron_variant	Intron 1 of 1	3		ENSP00000419517.1
PROX1-AS1	ENST00000433082.6	n.62+1116T>A		intron_variant	Intron 1 of 5	5
PROX1-AS1	ENST00000598091.1	n.51+375T>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70774 AN: 151878 Hom.: 17411 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.466 AC: 70790 AN: 151994 Hom.: 17410 Cov.: 32 AF XY: 0.463 AC XY: 34366 AN XY: 74276

African (AFR) AF: 0.293 AC: 12131 AN: 41460

American (AMR) AF: 0.506 AC: 7717 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3464

East Asian (EAS) AF: 0.571 AC: 2942 AN: 5148

South Asian (SAS) AF: 0.591 AC: 2842 AN: 4812

European-Finnish (FIN) AF: 0.452 AC: 4782 AN: 10576

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36972 AN: 67952

Other (OTH) AF: 0.459 AC: 969 AN: 2112

Alfa AF: 0.492 Hom.: 2358

Bravo AF: 0.461

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	-0.89
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs340872; hg19: chr1-214160548; COSMIC: COSV65293276;