21-45925731-C-G

Variant names:

• chr21-45925731-C-G
• rs395418
• NM_001384156.1:c.718-4186C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384156.1(PCBP3):​c.718-4186C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,126 control chromosomes in the GnomAD database, including 30,064 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 0.62 (30064 hom., cov: 33)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 2 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.718-4186C>G		intron_variant	Intron 13 of 17	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.718-4186C>G		intron_variant	Intron 13 of 17		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94393 AN: 152008 Hom.: 30031 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.621 AC: 94472 AN: 152126 Hom.: 30064 Cov.: 33 AF XY: 0.614 AC XY: 45655 AN XY: 74358

African (AFR) AF: 0.668 AC: 27714 AN: 41482

American (AMR) AF: 0.561 AC: 8576 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5178

South Asian (SAS) AF: 0.467 AC: 2251 AN: 4824

European-Finnish (FIN) AF: 0.593 AC: 6264 AN: 10558

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44303 AN: 68006

Other (OTH) AF: 0.597 AC: 1261 AN: 2112

Alfa AF: 0.627 Hom.: 3549

Bravo AF: 0.621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.50
PhyloP100		-0.73
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: rs395418; hg19: chr21-47345645;