rs2075423

Positions:

• chr1-213981376-G-T

Variant summary

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

The NR_037850.2(PROX1-AS1):​n.85+4693C>A variant causes a intron, non coding transcript change. The variant allele was found at a frequency of 0.359 in 147,070 control chromosomes in the GnomAD database, including 9,606 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 0.36 (9605 hom., cov: 24)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PROX1-AS1 NR_037850.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX1-AS1	NR_037850.2	n.85+4693C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX1-AS1	ENST00000433082.6	n.62+6945C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.359 AC: 52712 AN: 146948 Hom.: 9597 Cov.: 24

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.359 AC: 52751 AN: 147066 Hom.: 9605 Cov.: 24 AF XY: 0.362 AC XY: 25866 AN XY: 71364

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.377

Alfa AF: 0.353 Hom.: 6037

Bravo AF: 0.346

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.9
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075423; hg19: chr1-214154719; COSMIC: COSV71754325;