1-213989230-A-T

Variant names:

• chr1-213989230-A-T
• rs340838
• NM_001270616.2:c.-68+747A>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+747A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,378 control chromosomes in the GnomAD database, including 16,405 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 (16405 hom., cov: 29)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.-68+747A>T		intron_variant	Intron 1 of 4	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.-68+747A>T		intron_variant	Intron 1 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.-68+509A>T		intron_variant	Intron 1 of 4	1		ENSP00000400694.1
PROX1	ENST00000471129.1	c.-68+5907A>T		intron_variant	Intron 1 of 1	3		ENSP00000419517.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68359 AN: 151260 Hom.: 16406 Cov.: 29

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.452 AC: 68370 AN: 151378 Hom.: 16405 Cov.: 29 AF XY: 0.449 AC XY: 33197 AN XY: 73902

African (AFR) AF: 0.274 AC: 11297 AN: 41252

American (AMR) AF: 0.500 AC: 7622 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1670 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2885 AN: 5018

South Asian (SAS) AF: 0.587 AC: 2803 AN: 4776

European-Finnish (FIN) AF: 0.441 AC: 4626 AN: 10488

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35802 AN: 67836

Other (OTH) AF: 0.453 AC: 954 AN: 2104

Alfa AF: 0.468 Hom.: 2086

Bravo AF: 0.447

Asia WGS AF: 0.547 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.032
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs340838; hg19: chr1-214162573; COSMIC: COSV65293281; COSMIC: COSV65293281;