rs340877

Positions:

• chr1-213983903-G-A
• chr1-213983903-G-C
• chr1-213983903-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000610409.1(ENSG00000274895):​n.2517C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,114 control chromosomes in the GnomAD database, including 17,560 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 0.47 (17552 hom., cov: 33)
  • Exomes 𝑓: 0.50 (8 hom.)
• Consequence: ENST00000610409.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980

Genes affected

(HGNC:):

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

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROX1-AS1	NR_037850.2	n.85+2166C>T		intron_variant, non_coding_transcript_variant
PROX1	XM_011509773.3	c.-68+580G>A		intron_variant			XP_011508075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000610409.1	n.2517C>T		non_coding_transcript_exon_variant	1/1
PROX1-AS1	ENST00000433082.6	n.62+4418C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70800 AN: 151936 Hom.: 17550 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.500 AC: 30 AN: 60 Hom.: 8 Cov.: 0 AF XY: 0.500 AC XY: 18 AN XY: 36

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.466 AC: 70817 AN: 152054 Hom.: 17552 Cov.: 33 AF XY: 0.461 AC XY: 34271 AN XY: 74338

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.466

Alfa AF: 0.473 Hom.: 3765

Bravo AF: 0.462

Asia WGS AF: 0.535 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.96

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs340877; hg19: chr1-214157246;