rs4819143

Positions:

• chr21-45704264-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.-199-31128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,138 control chromosomes in the GnomAD database, including 2,901 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 0.17 (2901 hom., cov: 32)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

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]

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 (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.-199-31128G>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.-199-31128G>A		intron_variant			NM_001384156.1	ENSP00000505796	P4
PCBP3	ENST00000400314.5	c.-163-31128G>A		intron_variant		5		ENSP00000383168	P4
PCBP3	ENST00000465077.5	n.176-24412G>A		intron_variant, non_coding_transcript_variant		3
PCBP3	ENST00000594149.5	n.181+30529G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26375 AN: 152020 Hom.: 2898 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.00445

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.173 AC: 26387 AN: 152138 Hom.: 2901 Cov.: 32 AF XY: 0.174 AC XY: 12915 AN XY: 74348

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.00446

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.166

Alfa AF: 0.219 Hom.: 3333

Bravo AF: 0.163

Asia WGS AF: 0.0460 AC: 159 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	4.5
DANN	Benign	0.42

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: rs4819143; hg19: chr21-47124178;