rs12539410

Variant names:

• chr7-132381325-G-C
• rs12539410
• NM_020911.2:c.1372-83103C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020911.2(PLXNA4):​c.1372-83103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,220 control chromosomes in the GnomAD database, including 1,000 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (1000 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA4	NM_020911.2	c.1372-83103C>G		intron_variant	Intron 3 of 31	ENST00000321063.9	NP_065962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000321063.9	c.1372-83103C>G		intron_variant	Intron 3 of 31	5	NM_020911.2	ENSP00000323194.4
PLXNA4	ENST00000359827.7	c.1372-83103C>G		intron_variant	Intron 3 of 31	5		ENSP00000352882.3

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12542 AN: 152102 Hom.: 987 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0826 AC: 12576 AN: 152220 Hom.: 1000 Cov.: 33 AF XY: 0.0808 AC XY: 6013 AN XY: 74426

African (AFR) AF: 0.170 AC: 7078 AN: 41518

American (AMR) AF: 0.170 AC: 2604 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5186

South Asian (SAS) AF: 0.0242 AC: 117 AN: 4826

European-Finnish (FIN) AF: 0.0140 AC: 148 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0325 AC: 2211 AN: 68004

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0609 Hom.: 71

Bravo AF: 0.0988

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.089
DANN	Benign	0.46
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12539410; hg19: chr7-132066084;