7-132142002-A-T

Position:

• chr7-132142002-A-T

Variant summary

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

The NM_020911.2(PLXNA4):​c.5226-1191T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,184 control chromosomes in the GnomAD database, including 12,718 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 0.27 (12718 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA4	NM_020911.2	c.5226-1191T>A		intron_variant		ENST00000321063.9	NP_065962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000321063.9	c.5226-1191T>A		intron_variant		5	NM_020911.2	ENSP00000323194	P1
PLXNA4	ENST00000359827.7	c.5226-1191T>A		intron_variant		5		ENSP00000352882	P1
PLXNA4	ENST00000496550.1	n.390-1191T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40599 AN: 152066 Hom.: 12662 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.268 AC: 40719 AN: 152184 Hom.: 12718 Cov.: 32 AF XY: 0.264 AC XY: 19662 AN XY: 74430

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.0465

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.202

Alfa AF: 0.166 Hom.: 786

Bravo AF: 0.289

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.56
DANN	Benign	0.36

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: rs2671095; hg19: chr7-131826761;