rs11120242

Positions:

• chr1-214029344-A-C

Variant summary

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

The NM_001270616.2(PROX1):​c.2029-6305A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,290 control chromosomes in the GnomAD database, including 292 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 0.046 (292 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1	NM_001270616.2	c.2029-6305A>C		intron_variant		ENST00000366958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1	ENST00000366958.9	c.2029-6305A>C		intron_variant		1	NM_001270616.2	P1
PROX1	ENST00000435016.2	c.2029-6305A>C		intron_variant		1		P1
	ENST00000607258.2	n.1558T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6945 AN: 152166 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0458 AC: 6970 AN: 152284 Hom.: 292 Cov.: 32 AF XY: 0.0453 AC XY: 3376 AN XY: 74466

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0243 Hom.: 83

Bravo AF: 0.0466

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.90
DANN	Benign	0.28

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: rs11120242; hg19: chr1-214202687;