rs8127571

Positions:

• chr21-45745515-A-G
• chr21-45745515-A-T
• chr21-45745515-A-C

Variant summary

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

The NM_001384156.1(PCBP3):​c.-161-9902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,300 control chromosomes in the GnomAD database, including 64,564 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 0.92 (64564 hom., cov: 31)
• Consequence: PCBP3 NM_001384156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBP3	NM_001384156.1	c.-161-9902A>G		intron_variant		ENST00000681687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBP3	ENST00000681687.1	c.-161-9902A>G		intron_variant			NM_001384156.1	P4

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139933 AN: 152182 Hom.: 64503 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.920 AC: 140053 AN: 152300 Hom.: 64564 Cov.: 31 AF XY: 0.925 AC XY: 68871 AN XY: 74470

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.980

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.899

Alfa AF: 0.888 Hom.: 66465

Bravo AF: 0.920

Asia WGS AF: 0.984 AC: 3419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.71

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: rs8127571; hg19: chr21-47165429;