rs4655313

Positions:

• chr1-213993949-A-G

Variant summary

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

The NM_001270616.2(PROX1):​c.-67-2520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,222 control chromosomes in the GnomAD database, including 2,492 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 0.18 (2492 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.956

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 (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.-67-2520A>G		intron_variant		ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.-67-2520A>G		intron_variant		1	NM_001270616.2	ENSP00000355925	P1
PROX1	ENST00000435016.2	c.-67-2520A>G		intron_variant		1		ENSP00000400694	P1
PROX1	ENST00000471129.1	c.-67-2520A>G		intron_variant		3		ENSP00000419517
PROX1	ENST00000607425.1	c.-67-2520A>G		intron_variant		3		ENSP00000475357

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27059 AN: 152104 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.178 AC: 27064 AN: 152222 Hom.: 2492 Cov.: 32 AF XY: 0.179 AC XY: 13318 AN XY: 74426

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.179

Alfa AF: 0.183 Hom.: 602

Bravo AF: 0.186

Asia WGS AF: 0.152 AC: 528 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	9.8
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: rs4655313; hg19: chr1-214167292;