Variant chr7-132130551-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_020911.2(PLXNA4):c.5613T>C(p.Asp1871=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,613,950 control chromosomes in the GnomAD database, including 611,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.87 ( 58048 hom., cov: 32)

Exomes 𝑓: 0.87 ( 552990 hom. )

Consequence

PLXNA4
NM_020911.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.921

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-132130551-A-G is Benign according to our data. Variant chr7-132130551-A-G is described in ClinVar as [Benign]. Clinvar id is 3060996.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.921 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 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.5613T>C	p.Asp1871=	synonymous_variant	32/32	ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9 linkuse as main transcript	c.5613T>C	p.Asp1871=	synonymous_variant	32/32	5	NM_020911.2	P1	Q9HCM2-1
PLXNA4	ENST00000359827.7 linkuse as main transcript	c.5613T>C	p.Asp1871=	synonymous_variant	32/32	5		P1	Q9HCM2-1

Frequencies

GnomAD3 genomes

AF:

0.873

AC:

132763

AN:

152104

Hom.:

58002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.946

Gnomad SAS

AF:

0.923

Gnomad FIN

AF:

0.920

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.890

AC:

221851

AN:

249354

Hom.:

98853

AF XY:

0.889

AC XY:

120237

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.857

Gnomad AMR exome

AF:

0.936

Gnomad ASJ exome

AF:

0.867

Gnomad EAS exome

AF:

0.947

Gnomad SAS exome

AF:

0.921

Gnomad FIN exome

AF:

0.915

Gnomad NFE exome

AF:

0.860

Gnomad OTH exome

AF:

0.883

GnomAD4 exome

AF:

0.869

AC:

1270764

AN:

1461728

Hom.:

552990

Cov.:

AF XY:

0.870

AC XY:

632642

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.857

Gnomad4 AMR exome

AF:

0.934

Gnomad4 ASJ exome

AF:

0.865

Gnomad4 EAS exome

AF:

0.943

Gnomad4 SAS exome

AF:

0.918

Gnomad4 FIN exome

AF:

0.915

Gnomad4 NFE exome

AF:

0.858

Gnomad4 OTH exome

AF:

0.872

GnomAD4 genome

AF:

0.873

AC:

132868

AN:

152222

Hom.:

58048

Cov.:

AF XY:

0.878

AC XY:

65326

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.861

Gnomad4 AMR

AF:

0.900

Gnomad4 ASJ

AF:

0.876

Gnomad4 EAS

AF:

0.946

Gnomad4 SAS

AF:

0.922

Gnomad4 FIN

AF:

0.920

Gnomad4 NFE

AF:

0.857

Gnomad4 OTH

AF:

0.886

Alfa

AF:

0.863

Hom.:

66247

Bravo

AF:

0.871

Asia WGS

AF:

0.927

AC:

3221

AN:

3478

EpiCase

AF:

0.856

EpiControl

AF:

0.854

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

-0.81

CADD

Benign

0.23

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

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