Variant 7-132133064-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020911.2(PLXNA4):c.5574C>A(p.Gly1858=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,613,990 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 16 hom. )

Consequence

PLXNA4
NM_020911.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-132133064-G-T is Benign according to our data. Variant chr7-132133064-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041340.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BS2

High AC in GnomAd4 at 370 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2 linkuse as main transcript	c.5574C>A	p.Gly1858=	synonymous_variant	31/32	ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9 linkuse as main transcript	c.5574C>A	p.Gly1858=	synonymous_variant	31/32	5	NM_020911.2	P1	Q9HCM2-1
PLXNA4	ENST00000359827.7 linkuse as main transcript	c.5574C>A	p.Gly1858=	synonymous_variant	31/32	5		P1	Q9HCM2-1

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00331

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00235

AC:

586

AN:

249068

Hom.:

AF XY:

0.00255

AC XY:

345

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.00381

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00328

AC:

4797

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2346

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00333

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152280

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00387

Gnomad4 NFE

AF:

0.00331

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLXNA4-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 26, 2021

This variant is classified as likely 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

-0.52

CADD

Benign

7.5

DANN

Benign

0.61

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