Variant chr11-16791004-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_001329630.2(PLEKHA7):c.2934+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,010 control chromosomes in the GnomAD database, including 134 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 0.0058 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 113 hom. )

Consequence

PLEKHA7
NM_001329630.2 splice_region, intron

Scores

Splicing: ADA: 0.000009096

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.17

Variant links:

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA7 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=-0.89).

BP6

Variant 11-16791004-C-T is Benign according to our data. Variant chr11-16791004-C-T is described in ClinVar as [Benign]. Clinvar id is 773808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0058 (884/152294) while in subpopulation EAS AF= 0.0441 (228/5166). AF 95% confidence interval is 0.0394. There are 21 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2 linkuse as main transcript	c.2934+7G>A		splice_region_variant, intron_variant		ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6 linkuse as main transcript	c.2934+7G>A		splice_region_variant, intron_variant		5	NM_001329630.2	ENSP00000435389	A1

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

885

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0442

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00851

AC:

2135

AN:

250882

Hom.:

AF XY:

0.00816

AC XY:

1107

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.0485

Gnomad NFE exome

AF:

0.000979

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00325

AC:

4755

AN:

1461716

Hom.:

113

Cov.:

AF XY:

0.00319

AC XY:

2322

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0438

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.0448

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.00580

AC:

884

AN:

152294

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

626

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0441

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0551

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00215

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 17, 2018	- -

PLEKHA7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.15

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000091

dbscSNV1_RF

Benign

0.0

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