1-214006629-G-T

Variant names:

• chr1-214006629-G-T
• rs3754138
• NM_001270616.2:c.1833+1357G>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.1833+1357G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,966 control chromosomes in the GnomAD database, including 5,939 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 0.27 (5939 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794
• Publications: 4 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 = 0.382 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	NM_001270616.2	MANE Select	c.1833+1357G>T		intron	N/A	NP_001257545.1
	PROX1	NM_002763.5		c.1833+1357G>T		intron	N/A	NP_002754.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.1833+1357G>T		intron	N/A	ENSP00000355925.4
	PROX1	ENST00000435016.2	TSL:1	c.1833+1357G>T		intron	N/A	ENSP00000400694.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41631 AN: 151848 Hom.: 5927 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.274 AC: 41691 AN: 151966 Hom.: 5939 Cov.: 32 AF XY: 0.276 AC XY: 20490 AN XY: 74280

African (AFR) AF: 0.268 AC: 11098 AN: 41436

American (AMR) AF: 0.391 AC: 5966 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3464

East Asian (EAS) AF: 0.307 AC: 1585 AN: 5158

South Asian (SAS) AF: 0.161 AC: 777 AN: 4816

European-Finnish (FIN) AF: 0.276 AC: 2922 AN: 10568

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17604 AN: 67942

Other (OTH) AF: 0.280 AC: 589 AN: 2102

Alfa AF: 0.261 Hom.: 13572

Bravo AF: 0.285

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		0.79
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: rs3754138; hg19: chr1-214179972;