NM_020911.2:c.5225+750G>A

Variant names:

• chr7-132144369-C-T
• rs1399090
• NM_020911.2:c.5225+750G>A

Variant summary

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

The NM_020911.2(PLXNA4):​c.5225+750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,090 control chromosomes in the GnomAD database, including 12,394 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 (12394 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 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.5225+750G>A		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.5225+750G>A		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.5225+750G>A		intron	N/A	ENSP00000323194.4
	PLXNA4	ENST00000359827.7	TSL:5	c.5225+750G>A		intron	N/A	ENSP00000352882.3
	PLXNA4	ENST00000496550.1	TSL:4	n.389+750G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40059 AN: 151972 Hom.: 12346 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.264 AC: 40170 AN: 152090 Hom.: 12394 Cov.: 33 AF XY: 0.260 AC XY: 19333 AN XY: 74382

African (AFR) AF: 0.755 AC: 31313 AN: 41462

American (AMR) AF: 0.122 AC: 1867 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.0467 AC: 242 AN: 5182

South Asian (SAS) AF: 0.0731 AC: 352 AN: 4816

European-Finnish (FIN) AF: 0.126 AC: 1329 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4307 AN: 67990

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.132 Hom.: 11465

Bravo AF: 0.286

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.45
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1399090; hg19: chr7-131829128;