chr1-213990332-G-A

Position:

• chr1-213990332-G-A

Variant summary

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

The NM_001270616.2(PROX1):​c.-68+1849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 148,620 control chromosomes in the GnomAD database, including 11,426 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 0.38 (11426 hom., cov: 23)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.-68+1849G>A		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.-68+1849G>A		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.-68+1611G>A		intron_variant		1		P1
PROX1	ENST00000471129.1	c.-67-6137G>A		intron_variant		3
PROX1	ENST00000607425.1	c.-68+551G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 56193 AN: 148498 Hom.: 11424 Cov.: 23

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.378 AC: 56189 AN: 148620 Hom.: 11426 Cov.: 23 AF XY: 0.374 AC XY: 27061 AN XY: 72322

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.390

Alfa AF: 0.440 Hom.: 20508

Bravo AF: 0.368

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs340835; hg19: chr1-214163675; COSMIC: COSV65293297; COSMIC: COSV65293297;