rs3767848

Positions:

• chr1-214000497-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366958.9(PROX1):​c.1725+2237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,012 control chromosomes in the GnomAD database, including 8,696 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 0.32 (8696 hom., cov: 32)
• Consequence: PROX1 ENST00000366958.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.1725+2237G>A		intron_variant		ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.1725+2237G>A		intron_variant		1	NM_001270616.2	ENSP00000355925	P1
PROX1	ENST00000435016.2	c.1725+2237G>A		intron_variant		1		ENSP00000400694	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49284 AN: 151894 Hom.: 8667 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.325 AC: 49368 AN: 152012 Hom.: 8696 Cov.: 32 AF XY: 0.327 AC XY: 24270 AN XY: 74312

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.310

Alfa AF: 0.271 Hom.: 5836

Bravo AF: 0.340

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.044
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3767848; hg19: chr1-214173840;