rs7341474

chr7-132171454-C-G

Variant summary

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

The NM_020911.2(PLXNA4):c.4018-2882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,272 control chromosomes in the GnomAD database, including 434 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 0.063 (434 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2	c.4018-2882G>C		intron_variant		ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9	c.4018-2882G>C		intron_variant		5	NM_020911.2	P1
PLXNA4	ENST00000359827.7	c.4018-2882G>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9632 AN: 152154 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0634 AC: 9651 AN: 152272 Hom.: 434 Cov.: 33 AF XY: 0.0655 AC XY: 4873 AN XY: 74436

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0491

Alfa AF: 0.0754 Hom.: 75

Bravo AF: 0.0557

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs7341474; hg19: chr7-131856213;