rs340835

Variant names:

• chr1-213990332-G-A
• rs340835
• NM_001270616.2:c.-68+1849G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-213990332-G-A
• chr1-213990332-G-C
• chr1-213990332-G-T

Variant summary

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

The NM_001270616.2(PROX1):​c.-68+1849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 148,620 control chromosomes in the GnomAD database, including 11,426 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 0.38 (11426 hom., cov: 23)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 22 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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	NM_001270616.2	MANE Select	c.-68+1849G>A		intron	N/A	NP_001257545.1	Q92786
	PROX1	NM_002763.5		c.-68+1611G>A		intron	N/A	NP_002754.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.-68+1849G>A		intron	N/A	ENSP00000355925.4	Q92786
	PROX1	ENST00000435016.2	TSL:1	c.-68+1611G>A		intron	N/A	ENSP00000400694.1	Q92786
	PROX1	ENST00000881021.1		c.-68+1849G>A		intron	N/A	ENSP00000551080.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 56193 AN: 148498 Hom.: 11424 Cov.: 23

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.378 AC: 56189 AN: 148620 Hom.: 11426 Cov.: 23 AF XY: 0.374 AC XY: 27061 AN XY: 72322

African (AFR) AF: 0.219 AC: 8824 AN: 40254

American (AMR) AF: 0.362 AC: 5357 AN: 14816

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1487 AN: 3450

East Asian (EAS) AF: 0.380 AC: 1881 AN: 4948

South Asian (SAS) AF: 0.497 AC: 2307 AN: 4638

European-Finnish (FIN) AF: 0.362 AC: 3583 AN: 9902

Middle Eastern (MID) AF: 0.416 AC: 119 AN: 286

European-Non Finnish (NFE) AF: 0.465 AC: 31293 AN: 67358

Other (OTH) AF: 0.390 AC: 807 AN: 2070

Alfa AF: 0.433 Hom.: 25198

Bravo AF: 0.368

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		1.5
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: rs340835; hg19: chr1-214163675; COSMIC: COSV65293297; COSMIC: COSV65293297;