chr1-213998749-G-T

Position:

• chr1-213998749-G-T

Variant summary

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

The NM_001270616.2(PROX1):​c.1725+489G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,110 control chromosomes in the GnomAD database, including 3,990 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 0.21 (3990 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.1725+489G>T		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.1725+489G>T		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.1725+489G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31659 AN: 151992 Hom.: 3975 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.208 AC: 31708 AN: 152110 Hom.: 3990 Cov.: 32 AF XY: 0.208 AC XY: 15449 AN XY: 74364

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0491

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.172

Alfa AF: 0.194 Hom.: 1003

Bravo AF: 0.217

Asia WGS AF: 0.0710 AC: 247 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	0.95
DANN	Benign	0.74

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: rs11802122; hg19: chr1-214172092;