chr21-45892549-G-A

Position:

• chr21-45892549-G-A

Variant summary

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

The NM_001384156.1(PCBP3):​c.11-3659G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 142,736 control chromosomes in the GnomAD database, including 16,950 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 0.45 (16950 hom., cov: 27)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

Genes affected

PCBP3 (HGNC:8651): (poly(rC) binding protein 3) This gene encodes a member of the KH-domain protein subfamily. Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha-CPs play important roles in post-transcriptional activities and have different cellular distributions. The protein encoded by this gene lacks the nuclear localization signals found in other subfamily members. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

PCBP3 (HGNC:):

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 = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.11-3659G>A		intron_variant		ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.11-3659G>A		intron_variant			NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 64511 AN: 142628 Hom.: 16915 Cov.: 27

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.452 AC: 64581 AN: 142736 Hom.: 16950 Cov.: 27 AF XY: 0.446 AC XY: 30940 AN XY: 69434

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.422

Alfa AF: 0.449 Hom.: 1538

Bravo AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.64

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: rs2839037; hg19: chr21-47312463; COSMIC: COSV68407194; COSMIC: COSV68407194;