rs4655313

Variant names:

• chr1-213993949-A-G
• rs4655313
• NM_001270616.2:c.-67-2520A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.83).
• 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 rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.-67-2520A>G		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.-67-2520A>G		intron_variant	Intron 1 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.-67-2520A>G		intron_variant	Intron 1 of 4	1		ENSP00000400694.1
PROX1	ENST00000471129.1	c.-67-2520A>G		intron_variant	Intron 1 of 1	3		ENSP00000419517.1
PROX1	ENST00000607425.1	c.-67-2520A>G		intron_variant	Intron 1 of 1	3		ENSP00000475357.1

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

African (AFR) AF: 0.180 AC: 7489 AN: 41536

American (AMR) AF: 0.252 AC: 3864 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3472

East Asian (EAS) AF: 0.151 AC: 782 AN: 5186

South Asian (SAS) AF: 0.127 AC: 612 AN: 4818

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11280 AN: 67998

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.175 Hom.: 4071

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
PhyloP100		0.96
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: rs4655313; hg19: chr1-214167292;