1-214016440-A-G

Variant names:

• chr1-214016440-A-G
• rs446175
• NM_001270616.2:c.2028+4725A>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.2028+4725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,082 control chromosomes in the GnomAD database, including 35,728 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 0.68 (35728 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270616.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	NM_001270616.2	MANE Select	c.2028+4725A>G		intron	N/A	NP_001257545.1
	PROX1	NM_002763.5		c.2028+4725A>G		intron	N/A	NP_002754.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.2028+4725A>G		intron	N/A	ENSP00000355925.4
	PROX1	ENST00000435016.2	TSL:1	c.2028+4725A>G		intron	N/A	ENSP00000400694.1
	PROX1	ENST00000881021.1		c.2028+4725A>G		intron	N/A	ENSP00000551080.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103271 AN: 151964 Hom.: 35729 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.679 AC: 103302 AN: 152082 Hom.: 35728 Cov.: 32 AF XY: 0.679 AC XY: 50500 AN XY: 74352

African (AFR) AF: 0.566 AC: 23475 AN: 41478

American (AMR) AF: 0.593 AC: 9056 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2577 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3643 AN: 5158

South Asian (SAS) AF: 0.835 AC: 4031 AN: 4826

European-Finnish (FIN) AF: 0.715 AC: 7558 AN: 10576

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50540 AN: 67990

Other (OTH) AF: 0.684 AC: 1440 AN: 2106

Alfa AF: 0.694 Hom.: 12548

Bravo AF: 0.663

Asia WGS AF: 0.704 AC: 2447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.7
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: rs446175; hg19: chr1-214189783;