Variant 8-100705064-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002568.4(PABPC1):c.1688-8G>A 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 0.0141 in 1,599,886 control chromosomes in the GnomAD database, including 208 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 16 hom., cov: 33)

Exomes 𝑓: 0.015 ( 192 hom. )

Consequence

PABPC1
NM_002568.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0004181

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.327

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-100705064-C-T is Benign according to our data. Variant chr8-100705064-C-T is described in ClinVar as [Benign]. Clinvar id is 778031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0146 (21120/1447674) while in subpopulation NFE AF= 0.0172 (19002/1107308). AF 95% confidence interval is 0.017. There are 192 homozygotes in gnomad4_exome. There are 10153 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PABPC1	NM_002568.4 linkuse as main transcript	c.1688-8G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000318607.10
PABPC1	XM_005250861.4 linkuse as main transcript	c.1688-8G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PABPC1	XM_047421694.1 linkuse as main transcript	c.1688-8G>A	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.1688-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002568.4	P1	P11940-1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1359

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00926

AC:

2216

AN:

239200

Hom.:

AF XY:

0.00925

AC XY:

1195

AN XY:

129174

show subpopulations

Gnomad AFR exome

AF:

0.00262

Gnomad AMR exome

AF:

0.00759

Gnomad ASJ exome

AF:

0.00245

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0146

AC:

21120

AN:

1447674

Hom.:

192

Cov.:

AF XY:

0.0141

AC XY:

10153

AN XY:

719436

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00732

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00280

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00893

AC:

1359

AN:

152212

Hom.:

Cov.:

AF XY:

0.00871

AC XY:

648

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00847

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.3

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.024

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