rs4731889

Positions:

• chr7-132640550-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181775.4(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 NM_181775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PLXNA4	NM_181775.4	c.-87+5378T>C		intron_variant			NP_861440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000378539.5	c.-87+5378T>C		intron_variant		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

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.562

Alfa AF: 0.563 Hom.: 7466

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4731889; hg19: chr7-132325309;