1-214025252-C-G

Position:

• chr1-214025252-C-G

Variant summary

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

The NM_001270616.2(PROX1):​c.2029-10397C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,184 control chromosomes in the GnomAD database, including 788 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 0.069 (788 hom., cov: 33)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.2029-10397C>G		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.2029-10397C>G		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.2029-10397C>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10438 AN: 152066 Hom.: 777 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0689 AC: 10493 AN: 152184 Hom.: 788 Cov.: 33 AF XY: 0.0687 AC XY: 5112 AN XY: 74402

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0607

Alfa AF: 0.0490 Hom.: 70

Bravo AF: 0.0729

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.050
DANN	Benign	0.42

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: rs12092859; hg19: chr1-214198595;