rs12386622

chr7-132168842-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020911.2(PLXNA4):c.4018-270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,138 control chromosomes in the GnomAD database, including 7,535 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 0.26 (7535 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2	c.4018-270C>T		intron_variant		ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9	c.4018-270C>T		intron_variant		5	NM_020911.2	P1
PLXNA4	ENST00000359827.7	c.4018-270C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39684 AN: 152020 Hom.: 7508 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.261 AC: 39770 AN: 152138 Hom.: 7535 Cov.: 33 AF XY: 0.260 AC XY: 19308 AN XY: 74384

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.237

Alfa AF: 0.164 Hom.: 4926

Bravo AF: 0.273

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.6
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs12386622; hg19: chr7-131853601;