4-134141580-T-G

Variant names:

• chr4-134141580-T-G
• rs3980965
• ENST00000654404.1:n.979+668A>C

Variant summary

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

The ENST00000654404.1(ENSG00000251199):​n.979+668A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 150,898 control chromosomes in the GnomAD database, including 21,293 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 0.48 (21293 hom., cov: 32)
• Consequence: ENSG00000251199 ENST00000654404.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

ENSG00000251199 (HGNC:):

PABPC4L (HGNC:31955): (poly(A) binding protein cytoplasmic 4 like) Predicted to enable mRNA 3'-UTR binding activity; poly(A) binding activity; and poly(U) RNA binding activity. Predicted to be part of ribonucleoprotein complex. Predicted to be active in cytoplasmic stress granule; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC4L	XR_001741133.2	n.2014+24906A>C		intron_variant	Intron 2 of 7
PABPC4L	XR_001741134.2	n.1692+24906A>C		intron_variant	Intron 2 of 8
PABPC4L	XR_001741135.2	n.1692+24906A>C		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000251199	ENST00000654404.1	n.979+668A>C		intron_variant	Intron 6 of 7
ENSG00000251199	ENST00000658033.1	n.543+24906A>C		intron_variant	Intron 3 of 4
ENSG00000251199	ENST00000658435.1	n.412-38063A>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73083 AN: 150806 Hom.: 21249 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.485 AC: 73176 AN: 150898 Hom.: 21293 Cov.: 32 AF XY: 0.492 AC XY: 36250 AN XY: 73682

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.474

Alfa AF: 0.333 Hom.: 9043

Bravo AF: 0.510

Asia WGS AF: 0.784 AC: 2713 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3980965; hg19: chr4-135062735;