21-45704264-G-A

Variant names:

• chr21-45704264-G-A
• rs4819143
• NM_001384156.1:c.-199-31128G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384156.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	NM_001384156.1	MANE Select	c.-199-31128G>A		intron	N/A	NP_001371085.1
	PCBP3	NM_001348240.2		c.-199-31128G>A		intron	N/A	NP_001335169.1
	PCBP3	NM_001348239.2		c.-199-31128G>A		intron	N/A	NP_001335168.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.-199-31128G>A		intron	N/A	ENSP00000505796.1
	PCBP3	ENST00000400314.5	TSL:5	c.-163-31128G>A		intron	N/A	ENSP00000383168.1
	PCBP3	ENST00000465077.5	TSL:3	n.176-24412G>A		intron	N/A

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

African (AFR) AF: 0.0644 AC: 2675 AN: 41550

American (AMR) AF: 0.180 AC: 2752 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3470

East Asian (EAS) AF: 0.00446 AC: 23 AN: 5158

South Asian (SAS) AF: 0.101 AC: 487 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10572

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16244 AN: 67970

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.206 Hom.: 5971

Bravo AF: 0.163

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4819143; hg19: chr21-47124178;