Variant 7-132130584-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020911.2(PLXNA4):c.5590-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,613,362 control chromosomes in the GnomAD database, including 458,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.70 ( 38019 hom., cov: 32)

Exomes 𝑓: 0.76 ( 420886 hom. )

Consequence

PLXNA4
NM_020911.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008983

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.512

Variant links:

Genes affected

PLXNA4 (HGNC:9102): (plexin A4) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including axon guidance; positive regulation of axonogenesis; and regulation of GTPase activity. Predicted to act upstream of or within several processes, including nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in plasma membrane. Predicted to be part of semaphorin receptor complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLXNA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-132130584-G-A is Benign according to our data. Variant chr7-132130584-G-A is described in ClinVar as [Benign]. Clinvar id is 3060928.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2 linkuse as main transcript	c.5590-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9 linkuse as main transcript	c.5590-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_020911.2	P1	Q9HCM2-1
PLXNA4	ENST00000359827.7 linkuse as main transcript	c.5590-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5		P1	Q9HCM2-1

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

105929

AN:

151944

Hom.:

38001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.828

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.717

GnomAD3 exomes

AF:

0.737

AC:

183123

AN:

248586

Hom.:

68480

AF XY:

0.740

AC XY:

99826

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.641

Gnomad ASJ exome

AF:

0.744

Gnomad EAS exome

AF:

0.827

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.769

Gnomad OTH exome

AF:

0.742

GnomAD4 exome

AF:

0.757

AC:

1105717

AN:

1461300

Hom.:

420886

Cov.:

AF XY:

0.755

AC XY:

548620

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.747

Gnomad4 EAS exome

AF:

0.813

Gnomad4 SAS exome

AF:

0.684

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.768

Gnomad4 OTH exome

AF:

0.742

GnomAD4 genome

AF:

0.697

AC:

105999

AN:

152062

Hom.:

38019

Cov.:

AF XY:

0.701

AC XY:

52095

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.827

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.885

Gnomad4 NFE

AF:

0.767

Gnomad4 OTH

AF:

0.716

Alfa

AF:

0.722

Hom.:

12342

Bravo

AF:

0.675

Asia WGS

AF:

0.695

AC:

2419

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXNA4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

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

-0.72

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000090

dbscSNV1_RF

Benign

0.0040

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