1-213989391-G-T

Position:

• chr1-213989391-G-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+908G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,338 control chromosomes in the GnomAD database, including 16,253 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 0.45 (16253 hom., cov: 28)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.-68+908G>T		intron_variant		ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.-68+908G>T		intron_variant		1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.-68+670G>T		intron_variant		1		ENSP00000400694.1
PROX1	ENST00000471129.1	c.-68+6068G>T		intron_variant		3		ENSP00000419517.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68110 AN: 151220 Hom.: 16254 Cov.: 28

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.450 AC: 68125 AN: 151338 Hom.: 16253 Cov.: 28 AF XY: 0.447 AC XY: 33023 AN XY: 73872

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.452

Alfa AF: 0.468 Hom.: 2527

Bravo AF: 0.447

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs340837; hg19: chr1-214162734; COSMIC: COSV65293289; COSMIC: COSV65293289;