dbSNP rs340839: PROX1:c.-74G>A (chr1-213988477-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 NM_001270616.2(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
NM_001270616.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.30

Publications

23 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:

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=-0.3).

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 rank	MANE	Protein	UniProt
PROX1	NM_001270616.2 link	c.-74G>A		5_prime_UTR_variant	Exon 1 of 5	ENST00000366958.9	NP_001257545.1	Q92786

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9 link	c.-74G>A		5_prime_UTR_variant	Exon 1 of 5	1	NM_001270616.2	ENSP00000355925.4		Q92786
PROX1	ENST00000435016.2 link	c.-312G>A		upstream_gene_variant		1		ENSP00000400694.1		Q92786

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

62676

AN:

150492

Hom.:

13742

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.426

AC XY:

AN XY:

176

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.422

AC:

AN:

206

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.416

AC:

62682

AN:

150600

Hom.:

13739

Cov.:

AF XY:

0.413

AC XY:

30357

AN XY:

73478

show subpopulations

African (AFR)

AF:

0.266

AC:

10876

AN:

40868

American (AMR)

AF:

0.458

AC:

6955

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1602

AN:

3460

East Asian (EAS)

AF:

0.525

AC:

2627

AN:

5004

South Asian (SAS)

AF:

0.550

AC:

2618

AN:

4760

European-Finnish (FIN)

AF:

0.373

AC:

3822

AN:

10256

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32615

AN:

67772

Other (OTH)

AF:

0.428

AC:

895

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1700

3400

5100

6800

8500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.465

Hom.:

64432

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

(source)

DANN

Benign

0.93

PhyloP100

5.3

PromoterAI

-0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over