rs281877

Variant names:

• chr7-132136709-T-A
• rs281877
• NM_020911.2:c.5439-3510A>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.5439-3510A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,086 control chromosomes in the GnomAD database, including 6,291 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 0.25 (6291 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 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.5439-3510A>T		intron	N/A	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5439-3510A>T		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.5439-3510A>T		intron	N/A	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5439-3510A>T		intron	N/A	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5439-3510A>T		intron	N/A	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37835 AN: 151968 Hom.: 6283 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.249 AC: 37883 AN: 152086 Hom.: 6291 Cov.: 32 AF XY: 0.248 AC XY: 18460 AN XY: 74360

African (AFR) AF: 0.460 AC: 19059 AN: 41442

American (AMR) AF: 0.294 AC: 4497 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3470

East Asian (EAS) AF: 0.165 AC: 853 AN: 5178

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4820

European-Finnish (FIN) AF: 0.0786 AC: 834 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10008 AN: 67968

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.212 Hom.: 592

Bravo AF: 0.271

Asia WGS AF: 0.286 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		0.13
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: rs281877; hg19: chr7-131821468;