1-213985643-G-C

Variant names:

• chr1-213985643-G-C
• rs340875
• ENST00000471129.1:c.-68+2320G>C

Variant summary

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

The ENST00000471129.1(PROX1):​c.-68+2320G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,192 control chromosomes in the GnomAD database, including 14,611 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 0.43 (14610 hom., cov: 34)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PROX1 ENST00000471129.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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]

ENSG00000274895 (HGNC:):

PROX1-AS1 (HGNC:43656): (PROX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	XM_011509773.3	c.-68+2320G>C		intron_variant	Intron 1 of 4		XP_011508075.1
PROX1-AS1	NR_037850.2	n.85+426C>G		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000471129.1	c.-68+2320G>C		intron_variant	Intron 1 of 1	3		ENSP00000419517.1
ENSG00000274895	ENST00000610409.1	n.777C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
PROX1-AS1	ENST00000433082.6	n.62+2678C>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64804 AN: 152068 Hom.: 14612 Cov.: 34

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.426 AC: 64815 AN: 152186 Hom.: 14610 Cov.: 34 AF XY: 0.422 AC XY: 31412 AN XY: 74392

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.431

Alfa AF: 0.447 Hom.: 1959

Bravo AF: 0.423

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs340875; hg19: chr1-214158986; COSMIC: COSV65293272;