Genetic Variant PLXNA4:c.5590-10C>T (chr7-132130584-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020911.2(PLXNA4):c.5590-10C>T variant causes a 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 intron

Scores

Splicing: ADA: 0.00008983

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.512

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020911.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	NM_020911.2	MANE Select	c.5590-10C>T		intron	N/A	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5590-10C>T		intron	N/A	NP_001380826.1	Q9HCM2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.5590-10C>T	intron	N/A	ENSP00000323194.4	Q9HCM2-1
PLXNA4	ENST00000359827.7	TSL:5	c.5590-10C>T	intron	N/A	ENSP00000352882.3	Q9HCM2-1
PLXNA4	ENST00000948949.1		c.5590-10C>T	intron	N/A	ENSP00000619008.1

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

GnomAD2 exomes

AF:

0.737

AC:

183123

AN:

248586

AF XY:

0.740

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 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

African (AFR)

AF:

0.518

AC:

17341

AN:

33470

American (AMR)

AF:

0.641

AC:

28648

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

19514

AN:

26130

East Asian (EAS)

AF:

0.813

AC:

32270

AN:

39692

South Asian (SAS)

AF:

0.684

AC:

59035

AN:

86246

European-Finnish (FIN)

AF:

0.878

AC:

46862

AN:

53374

Middle Eastern (MID)

AF:

0.702

AC:

4050

AN:

5766

European-Non Finnish (NFE)

AF:

0.768

AC:

853185

AN:

1111522

Other (OTH)

AF:

0.742

AC:

44812

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

14505

29011

43516

58022

72527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20404

40808

61212

81616

102020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.697

AC:

105999

AN:

152062

Hom.:

38019

Cov.:

AF XY:

0.701

AC XY:

52095

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.525

AC:

21754

AN:

41424

American (AMR)

AF:

0.657

AC:

10045

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.748

AC:

2596

AN:

3472

East Asian (EAS)

AF:

0.827

AC:

4263

AN:

5152

South Asian (SAS)

AF:

0.694

AC:

3343

AN:

4816

European-Finnish (FIN)

AF:

0.885

AC:

9376

AN:

10600

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.767

AC:

52180

AN:

67992

Other (OTH)

AF:

0.716

AC:

1514

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1527

3055

4582

6110

7637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.713

Hom.:

24812

Bravo

AF:

0.675

Asia WGS

AF:

0.695

AC:

2419

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLXNA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over