rs2425688

Positions:

• chr20-44922979-G-A
• chr20-44922979-G-C

Variant summary

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

The NM_001372179.1(PABPC1L):​c.877-1182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,142 control chromosomes in the GnomAD database, including 34,010 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 0.67 (34010 hom., cov: 32)
• Consequence: PABPC1L NM_001372179.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

PABPC1L (HGNC:15797): (poly(A) binding protein cytoplasmic 1 like) This gene belongs to the polyadenylate-binding protein type-1 family of proteins. Members of this family bind to the polyA tails of mRNAs to regulate mRNA stability and translation. The mouse ortholog of this gene is required for female fertility. In human, expression of a functional protein is regulated by alternative splicing. The protein-coding splice variant for this gene is abundantly expressed in human oocytes, while a noncoding splice variant subject to nonsense-mediated decay is the predominant splice variant expressed in somatic tissues. [provided by RefSeq, Aug 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC1L	NM_001372179.1	c.877-1182G>A		intron_variant		ENST00000217073.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1L	ENST00000217073.7	c.877-1182G>A		intron_variant		5	NM_001372179.1	P4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101098 AN: 152024 Hom.: 33969 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.665 AC: 101197 AN: 152142 Hom.: 34010 Cov.: 32 AF XY: 0.667 AC XY: 49603 AN XY: 74354

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.683

Alfa AF: 0.632 Hom.: 40051

Bravo AF: 0.665

Asia WGS AF: 0.619 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.27

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: rs2425688; hg19: chr20-43551620; COSMIC: COSV53839513;