chr7-132446355-C-A

Variant names:

• chr7-132446355-C-A
• rs2288986
• NM_020911.2:c.1371+42937G>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.1371+42937G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 152,252 control chromosomes in the GnomAD database, including 322 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 0.036 (322 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 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.1371+42937G>T		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.1371+42937G>T		intron	N/A	NP_001380826.1
	PLXNA4	NM_001105543.2		c.1371+42937G>T		intron	N/A	NP_001099013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.1371+42937G>T		intron	N/A	ENSP00000323194.4
	PLXNA4	ENST00000359827.7	TSL:5	c.1371+42937G>T		intron	N/A	ENSP00000352882.3
	PLXNA4	ENST00000423507.6	TSL:2	c.1371+42937G>T		intron	N/A	ENSP00000392772.2

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5439 AN: 152134 Hom.: 321 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00738

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0357 AC: 5440 AN: 152252 Hom.: 322 Cov.: 32 AF XY: 0.0377 AC XY: 2809 AN XY: 74444

African (AFR) AF: 0.0609 AC: 2527 AN: 41528

American (AMR) AF: 0.0184 AC: 281 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1478 AN: 5180

South Asian (SAS) AF: 0.0662 AC: 319 AN: 4818

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00738 AC: 502 AN: 68020

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0250 Hom.: 14

Bravo AF: 0.0373

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		-0.17
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: rs2288986; hg19: chr7-132131114;