rs7543057

Positions:

• chr1-214024336-T-C

Variant summary

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

The NM_001270616.2(PROX1):​c.2029-11313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,106 control chromosomes in the GnomAD database, including 4,295 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 0.17 (4295 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.2029-11313T>C		intron_variant		ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.2029-11313T>C		intron_variant		1	NM_001270616.2	ENSP00000355925	P1
PROX1	ENST00000435016.2	c.2029-11313T>C		intron_variant		1		ENSP00000400694	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25590 AN: 151986 Hom.: 4270 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.169 AC: 25686 AN: 152106 Hom.: 4295 Cov.: 32 AF XY: 0.169 AC XY: 12595 AN XY: 74364

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0667 Hom.: 1092

Bravo AF: 0.192

Asia WGS AF: 0.179 AC: 621 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	0.11
DANN	Benign	0.54

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: rs7543057; hg19: chr1-214197679;