chr1-213989726-C-T

Position:

• chr1-213989726-C-T

Variant summary

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

The NM_001270616.2(PROX1):​c.-68+1243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,092 control chromosomes in the GnomAD database, including 17,315 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 0.47 (17273 hom., cov: 29)
  • Exomes 𝑓: 0.49 (42 hom.)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.-68+1243C>T		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.-68+1243C>T		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.-68+1005C>T		intron_variant		1		P1
PROX1	ENST00000607425.1	c.-123C>T		5_prime_UTR_variant	1/2	3
PROX1	ENST00000471129.1	c.-68+6403C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71185 AN: 151664 Hom.: 17269 Cov.: 29

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.487 AC: 151 AN: 310 Hom.: 42 Cov.: 0 AF XY: 0.482 AC XY: 109 AN XY: 226

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.469 AC: 71207 AN: 151782 Hom.: 17273 Cov.: 29 AF XY: 0.466 AC XY: 34565 AN XY: 74162

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.464

Alfa AF: 0.493 Hom.: 3740

Bravo AF: 0.468

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs340836; hg19: chr1-214163069; COSMIC: COSV65293293; COSMIC: COSV65293293;