rs4655482

Variant names:

• chr1-214012941-G-A
• rs4655482
• NM_001270616.2:c.2028+1226G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-214012941-G-A
• chr1-214012941-G-C
• chr1-214012941-G-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.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
• Publications: 1 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=-0.87).
• 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 rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.2028+1226G>A		intron_variant	Intron 4 of 4	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.2028+1226G>A		intron_variant	Intron 4 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.2028+1226G>A		intron_variant	Intron 4 of 4	1		ENSP00000400694.1

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

African (AFR) AF: 0.110 AC: 4555 AN: 41368

American (AMR) AF: 0.154 AC: 2348 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.120 AC: 621 AN: 5168

South Asian (SAS) AF: 0.0715 AC: 344 AN: 4808

European-Finnish (FIN) AF: 0.00904 AC: 95 AN: 10504

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0204 AC: 1389 AN: 67932

Other (OTH) AF: 0.0651 AC: 137 AN: 2104

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4655482; hg19: chr1-214186284;