dbSNP rs340877: PROX1:c.-68+975G>A (chr1-213983903-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000471129.1(PROX1):c.-68+580G>A 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 152,114 control chromosomes in the GnomAD database, including 17,560 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 ( 17552 hom., cov: 33)

Exomes 𝑓: 0.50 ( 8 hom. )

Consequence

PROX1
ENST00000471129.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.980

Publications

9 publications found

Variant links:

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 links:

ENSG00000274895 (HGNC:):

ENSG00000274895 links:

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

PROX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1-AS1	NR_037850.2		n.85+2166C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PROX1	ENST00000881019.1		c.-68+975G>A	intron	N/A	ENSP00000551078.1
PROX1	ENST00000471129.1	TSL:3	c.-68+580G>A	intron	N/A	ENSP00000419517.1
ENSG00000274895	ENST00000610409.1	TSL:6	n.2517C>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70800

AN:

151936

Hom.:

17550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.479

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.466

AC:

70817

AN:

152054

Hom.:

17552

Cov.:

AF XY:

0.461

AC XY:

34271

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.282

AC:

11681

AN:

41492

American (AMR)

AF:

0.512

AC:

7826

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1723

AN:

3470

East Asian (EAS)

AF:

0.531

AC:

2739

AN:

5156

South Asian (SAS)

AF:

0.585

AC:

2817

AN:

4816

European-Finnish (FIN)

AF:

0.429

AC:

4534

AN:

10578

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37842

AN:

67944

Other (OTH)

AF:

0.466

AC:

984

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1861

3722

5582

7443

9304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.514

Hom.:

8390

Bravo

AF:

0.462

Asia WGS

AF:

0.535

AC:

1861

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.98

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over