rs4731889

Variant names:

• chr7-132640550-A-G
• rs4731889
• ENST00000378539.5:c.-87+5378T>C

Variant summary

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

The ENST00000378539.5(PLXNA4):​c.-87+5378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,064 control chromosomes in the GnomAD database, including 24,405 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 0.56 (24405 hom., cov: 32)
• Consequence: PLXNA4 ENST00000378539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA4	NM_181775.4	c.-87+5378T>C		intron_variant	Intron 2 of 4		NP_861440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000378539.5	c.-87+5378T>C		intron_variant	Intron 2 of 4	1		ENSP00000367800.5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85407 AN: 151944 Hom.: 24368 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.562 AC: 85499 AN: 152064 Hom.: 24405 Cov.: 32 AF XY: 0.557 AC XY: 41392 AN XY: 74352

African (AFR) AF: 0.611 AC: 25346 AN: 41478

American (AMR) AF: 0.561 AC: 8568 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2011 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1983 AN: 5166

South Asian (SAS) AF: 0.351 AC: 1694 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6153 AN: 10576

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38005 AN: 67950

Other (OTH) AF: 0.562 AC: 1186 AN: 2110

Alfa AF: 0.565 Hom.: 19292

Bravo AF: 0.567

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4731889; hg19: chr7-132325309;