chr21-45745515-A-G

Variant names:

• chr21-45745515-A-G
• rs8127571
• NM_001384156.1:c.-161-9902A>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.-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
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.-161-9902A>G		intron	N/A	NP_001371085.1
	PCBP3	NM_001348240.2		c.-161-9902A>G		intron	N/A	NP_001335169.1
	PCBP3	NM_001348239.2		c.-161-9902A>G		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.-161-9902A>G		intron	N/A	ENSP00000505796.1
	PCBP3	ENST00000400314.5	TSL:5	c.-126+10086A>G		intron	N/A	ENSP00000383168.1
	PCBP3	ENST00000465077.5	TSL:3	n.286+10086A>G		intron	N/A

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

African (AFR) AF: 0.978 AC: 40631 AN: 41558

American (AMR) AF: 0.918 AC: 14058 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3074 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.980 AC: 4721 AN: 4818

European-Finnish (FIN) AF: 0.931 AC: 9885 AN: 10622

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59514 AN: 68024

Other (OTH) AF: 0.899 AC: 1896 AN: 2110

Alfa AF: 0.893 Hom.: 119620

Bravo AF: 0.920

Asia WGS AF: 0.984 AC: 3419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.71
PhyloP100		-1.1
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: rs8127571; hg19: chr21-47165429;