rs726334

Variant names:

• chr1-214006775-G-A
• rs726334
• NM_001270616.2:c.1833+1503G>A

Variant summary

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

The NM_001270616.2(PROX1):​c.1833+1503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,692 control chromosomes in the GnomAD database, including 5,937 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 0.28 (5937 hom., cov: 33)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270616.2. 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
	PROX1	NM_001270616.2	MANE Select	c.1833+1503G>A		intron	N/A	NP_001257545.1
	PROX1	NM_002763.5		c.1833+1503G>A		intron	N/A	NP_002754.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.1833+1503G>A		intron	N/A	ENSP00000355925.4
	PROX1	ENST00000435016.2	TSL:1	c.1833+1503G>A		intron	N/A	ENSP00000400694.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41663 AN: 151574 Hom.: 5925 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.275 AC: 41723 AN: 151692 Hom.: 5937 Cov.: 33 AF XY: 0.277 AC XY: 20510 AN XY: 74154

African (AFR) AF: 0.269 AC: 11101 AN: 41228

American (AMR) AF: 0.390 AC: 5949 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1591 AN: 5158

South Asian (SAS) AF: 0.162 AC: 779 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2926 AN: 10538

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17631 AN: 67914

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.261 Hom.: 3361

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.053
DANN	Benign	0.29
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs726334; hg19: chr1-214180118;