rs340874

Positions:

• chr1-213985913-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471129.1(PROX1):​c.-68+2590T>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 ENST00000471129.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	XM_011509773.3	c.-68+2590T>C		intron_variant			XP_011508075.1
PROX1-AS1	NR_037850.2	n.85+156A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000471129.1	c.-68+2590T>C		intron_variant		3		ENSP00000419517.1
ENSG00000274895	ENST00000610409.1	n.507A>G		non_coding_transcript_exon_variant	1/1	6
PROX1-AS1	ENST00000433082.6	n.62+2408A>G		intron_variant		5

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

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.437

Alfa AF: 0.516 Hom.: 35649

Bravo AF: 0.398

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs340874; hg19: chr1-214159256;