Variant 8-100717892-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002568.4(PABPC1):c.388-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000576 in 1,460,622 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 6 hom. )

Consequence

PABPC1
NM_002568.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001110

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

PABPC1 (HGNC:8554): (poly(A) binding protein cytoplasmic 1) This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.[provided by RefSeq, Aug 2010]

PABPC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 8-100717892-G-A is Benign according to our data. Variant chr8-100717892-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 731563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PABPC1	NM_002568.4 linkuse as main transcript	c.388-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000318607.10
PABPC1	XM_005250861.4 linkuse as main transcript	c.388-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PABPC1	XM_047421694.1 linkuse as main transcript	c.388-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1	ENST00000318607.10 linkuse as main transcript	c.388-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002568.4	P1	P11940-1

Frequencies

GnomAD3 genomes

AF:

0.000610

AC:

AN:

150938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0220

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00106

AC:

261

AN:

246164

Hom.:

AF XY:

0.000954

AC XY:

127

AN XY:

133180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000332

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.000572

AC:

749

AN:

1309684

Hom.:

Cov.:

AF XY:

0.000611

AC XY:

395

AN XY:

646996

show subpopulations

Gnomad4 AFR exome

AF:

0.0000345

Gnomad4 AMR exome

AF:

0.0000554

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.000610

AC:

AN:

150938

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

AN XY:

73582

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0220

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.000616

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	PABPC1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over