rs4533449

Positions:

• chr2-11365087-T-C
• chr2-11365087-T-G

Variant summary

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

The XM_047446546.1(PPIAP60):​c.502-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,230 control chromosomes in the GnomAD database, including 37,590 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 0.70 (37547 hom., cov: 31)
  • Exomes 𝑓: 0.84 (43 hom.)
• Consequence: PPIAP60 XM_047446546.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

Genes affected

PPIAP60 (HGNC:):

LINC03037 (HGNC:56227): (long intergenic non-protein coding RNA 3037)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIAP60	XM_047446546.1	c.502-59T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC03037	ENST00000430897.1	n.539+11A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105968 AN: 151988 Hom.: 37495 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.844 AC: 103 AN: 122 Hom.: 43 Cov.: 0 AF XY: 0.829 AC XY: 58 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.878

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.697 AC: 106073 AN: 152108 Hom.: 37547 Cov.: 31 AF XY: 0.700 AC XY: 52054 AN XY: 74340

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.650

Alfa AF: 0.719 Hom.: 78830

Bravo AF: 0.686

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4533449; hg19: chr2-11505213;