rs4728251

Variant names:

• chr7-132143577-C-T
• rs4728251
• NM_020911.2:c.5225+1542G>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+1542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,032 control chromosomes in the GnomAD database, including 18,180 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 0.45 (18180 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	NM_020911.2	MANE Select	c.5225+1542G>A		intron	N/A	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5225+1542G>A		intron	N/A	NP_001380826.1	Q9HCM2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.5225+1542G>A		intron	N/A	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5225+1542G>A		intron	N/A	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5225+1542G>A		intron	N/A	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67716 AN: 151914 Hom.: 18193 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.445 AC: 67692 AN: 152032 Hom.: 18180 Cov.: 32 AF XY: 0.449 AC XY: 33324 AN XY: 74294

African (AFR) AF: 0.133 AC: 5529 AN: 41476

American (AMR) AF: 0.456 AC: 6966 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2010 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3749 AN: 5146

South Asian (SAS) AF: 0.511 AC: 2461 AN: 4812

European-Finnish (FIN) AF: 0.597 AC: 6303 AN: 10566

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38954 AN: 67968

Other (OTH) AF: 0.488 AC: 1031 AN: 2112

Alfa AF: 0.525 Hom.: 28895

Bravo AF: 0.426

Asia WGS AF: 0.522 AC: 1810 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.57
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: rs4728251; hg19: chr7-131828336;