rs10494972

Positions:

• chr1-214034008-T-A

Variant summary

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

The NM_001270616.2(PROX1):​c.2029-1641T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,146 control chromosomes in the GnomAD database, including 2,279 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 0.13 (2279 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.2029-1641T>A		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.2029-1641T>A		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.2029-1641T>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19854 AN: 152028 Hom.: 2266 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.131 AC: 19926 AN: 152146 Hom.: 2279 Cov.: 32 AF XY: 0.132 AC XY: 9850 AN XY: 74396

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0881 Hom.: 165

Bravo AF: 0.149

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.77

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: rs10494972; hg19: chr1-214207351;