7-132168842-G-A

Variant names:

• chr7-132168842-G-A
• rs12386622
• NM_020911.2:c.4018-270C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	NM_020911.2	MANE Select	c.4018-270C>T		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.4018-270C>T		intron	N/A	NP_001380826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.4018-270C>T		intron	N/A	ENSP00000323194.4
	PLXNA4	ENST00000359827.7	TSL:5	c.4018-270C>T		intron	N/A	ENSP00000352882.3

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

African (AFR) AF: 0.538 AC: 22306 AN: 41482

American (AMR) AF: 0.177 AC: 2700 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.0341 AC: 176 AN: 5162

South Asian (SAS) AF: 0.173 AC: 835 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1921 AN: 10608

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10615 AN: 67980

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.181 Hom.: 14785

Bravo AF: 0.273

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-0.19
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: rs12386622; hg19: chr7-131853601;