1-214013919-G-C

Variant names:

• chr1-214013919-G-C
• rs366684
• NM_001270616.2:c.2028+2204G>C

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+2204G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,020 control chromosomes in the GnomAD database, including 38,741 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 0.71 (38741 hom., cov: 31)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.2028+2204G>C		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+2204G>C		intron_variant	Intron 4 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.2028+2204G>C		intron_variant	Intron 4 of 4	1		ENSP00000400694.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108087 AN: 151902 Hom.: 38727 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.711 AC: 108145 AN: 152020 Hom.: 38741 Cov.: 31 AF XY: 0.710 AC XY: 52768 AN XY: 74284

African (AFR) AF: 0.677 AC: 28059 AN: 41454

American (AMR) AF: 0.607 AC: 9263 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2581 AN: 3470

East Asian (EAS) AF: 0.691 AC: 3554 AN: 5142

South Asian (SAS) AF: 0.837 AC: 4034 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7655 AN: 10572

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.743 AC: 50526 AN: 67996

Other (OTH) AF: 0.707 AC: 1488 AN: 2106

Alfa AF: 0.714 Hom.: 4573

Bravo AF: 0.699

Asia WGS AF: 0.712 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.59
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs366684; hg19: chr1-214187262; COSMIC: COSV54777172;