Variant 7-132133091-T-C 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.5547A>G(p.Ala1849Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,040 control chromosomes in the GnomAD database, including 11,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.093 ( 961 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10522 hom. )

Consequence

PLXNA4
NM_020911.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.95

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=-0.92).

BP6

Variant 7-132133091-T-C is Benign according to our data. Variant chr7-132133091-T-C is described in ClinVar as [Benign]. Clinvar id is 3059020.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA4	NM_020911.2 linkuse as main transcript	c.5547A>G	p.Ala1849Ala	synonymous_variant	31/32	ENST00000321063.9	NP_065962.1	Q9HCM2-1A0A024R7A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000321063.9 linkuse as main transcript	c.5547A>G	p.Ala1849Ala	synonymous_variant	31/32	5	NM_020911.2	ENSP00000323194.4		Q9HCM2-1
PLXNA4	ENST00000359827.7 linkuse as main transcript	c.5547A>G	p.Ala1849Ala	synonymous_variant	31/32	5		ENSP00000352882.3		Q9HCM2-1

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14194

AN:

152078

Hom.:

952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0951

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.131

AC:

32707

AN:

249408

Hom.:

3035

AF XY:

0.131

AC XY:

17728

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.0359

Gnomad NFE exome

AF:

0.0969

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.109

AC:

158886

AN:

1461844

Hom.:

10522

Cov.:

AF XY:

0.111

AC XY:

81059

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.0983

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.0933

AC:

14206

AN:

152196

Hom.:

961

Cov.:

AF XY:

0.0961

AC XY:

7153

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.0348

Gnomad4 NFE

AF:

0.0951

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0941

Hom.:

429

Bravo

AF:

0.103

Asia WGS

AF:

0.204

AC:

707

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.106

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

-0.92

CADD

Benign

0.12

DANN

Benign

0.39

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