14-74860740-T-C

Position:

• chr14-74860740-T-C

Variant summary

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

The ENST00000556489.4(PROX2):​c.1305+1790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,974 control chromosomes in the GnomAD database, including 16,315 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 0.45 (16315 hom., cov: 32)
• Consequence: PROX2 ENST00000556489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

Genes affected

PROX2 (HGNC:26715): (prospero homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX2	NM_001243007.2	c.1305+1790A>G		intron_variant		ENST00000556489.4	NP_001229936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROX2	ENST00000556489.4	c.1305+1790A>G		intron_variant		1	NM_001243007.2	ENSP00000451223	P1
PROX2	ENST00000673765.1	c.732+2363A>G		intron_variant				ENSP00000501015

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68302 AN: 151856 Hom.: 16292 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.450 AC: 68365 AN: 151974 Hom.: 16315 Cov.: 32 AF XY: 0.446 AC XY: 33160 AN XY: 74270

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.451

Alfa AF: 0.396 Hom.: 11949

Bravo AF: 0.450

Asia WGS AF: 0.367 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.69

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: rs722599; hg19: chr14-75327443;