rs10490413

Positions:

• chr2-71211489-C-T

Variant summary

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

The NM_020459.1(PAIP2B):​c.-11-8889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,498 control chromosomes in the GnomAD database, including 4,959 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 0.23 (4959 hom., cov: 30)
• Consequence: PAIP2B NM_020459.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

PAIP2B (HGNC:29200): (poly(A) binding protein interacting protein 2B) Most mRNAs, except for histones, contain a 3-prime poly(A) tail. Poly(A)-binding protein (PABP; see MIM 604679) enhances translation by circularizing mRNA through its interaction with the translation initiation factor EIF4G1 (MIM 600495) and the poly(A) tail. Various PABP-binding proteins regulate PABP activity, including PAIP1 (MIM 605184), a translational stimulator, and PAIP2A (MIM 605604) and PAIP2B, translational inhibitors (Derry et al., 2006 [PubMed 17381337]).[supplied by OMIM, Mar 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAIP2B	NM_020459.1	c.-11-8889G>A		intron_variant		ENST00000244221.9	NP_065192.1
PAIP2B	XM_011532842.4	c.53-8889G>A		intron_variant			XP_011531144.1
PAIP2B	XM_005264310.5	c.-11-8889G>A		intron_variant			XP_005264367.1
PAIP2B	XM_005264311.5	c.-11-8889G>A		intron_variant			XP_005264368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAIP2B	ENST00000244221.9	c.-11-8889G>A		intron_variant		1	NM_020459.1	ENSP00000244221.8

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35535 AN: 151374 Hom.: 4952 Cov.: 30

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35562 AN: 151498 Hom.: 4959 Cov.: 30 AF XY: 0.231 AC XY: 17054 AN XY: 73958

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.227

Alfa AF: 0.215 Hom.: 634

Bravo AF: 0.237

Asia WGS AF: 0.0770 AC: 272 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	6.1
DANN	Benign	0.63

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: rs10490413; hg19: chr2-71438619;