rs4655482

chr1-214012941-G-Achr1-214012941-G-Cchr1-214012941-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.2028+1226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 151,794 control chromosomes in the GnomAD database, including 536 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 0.063 (536 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.2028+1226G>A		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.2028+1226G>A		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.2028+1226G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9532 AN: 151676 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0672

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

GnomAD4 genome AF: 0.0630 AC: 9556 AN: 151794 Hom.: 536 Cov.: 32 AF XY: 0.0651 AC XY: 4827 AN XY: 74160

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.0651

Alfa AF: 0.0155 Hom.: 10

Bravo AF: 0.0774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.80
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4655482; hg19: chr1-214186284;