ENST00000881019.1:c.-68+2985T>C

Variant names:

• chr1-213985913-T-C
• rs340874
• ENST00000881019.1:c.-68+2985T>C

Variant summary

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

The ENST00000881019.1(PROX1):​c.-68+2985T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,950 control chromosomes in the GnomAD database, including 14,774 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 0.41 (14770 hom., cov: 31)
  • Exomes 𝑓: 0.56 (4 hom.)
• Consequence: PROX1 ENST00000881019.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 221 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]

ENSG00000274895 (HGNC:):

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000881019.1. 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+156A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000881019.1		c.-68+2985T>C		intron	N/A	ENSP00000551078.1
	PROX1	ENST00000471129.1	TSL:3	c.-68+2590T>C		intron	N/A	ENSP00000419517.1
	ENSG00000274895	ENST00000610409.1	TSL:6	n.507A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62269 AN: 151796 Hom.: 14766 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.556 AC: 20 AN: 36 Hom.: 4 Cov.: 0 AF XY: 0.607 AC XY: 17 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.458 AC: 11 AN: 24

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.410 AC: 62259 AN: 151914 Hom.: 14770 Cov.: 31 AF XY: 0.405 AC XY: 30041 AN XY: 74216

African (AFR) AF: 0.166 AC: 6878 AN: 41442

American (AMR) AF: 0.416 AC: 6348 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1616 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2047 AN: 5146

South Asian (SAS) AF: 0.530 AC: 2546 AN: 4800

European-Finnish (FIN) AF: 0.407 AC: 4285 AN: 10532

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36937 AN: 67946

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.502 Hom.: 76561

Bravo AF: 0.398

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.9
DANN	Benign	0.77
PhyloP100		-0.099

Splicing

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

Other links and lift over

dbSNP: rs340874; hg19: chr1-214159256;