chr7-132339024-T-A

Variant names:

• chr7-132339024-T-A
• rs4731863
• NM_020911.2:c.1372-40802A>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.1372-40802A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,188 control chromosomes in the GnomAD database, including 1,003 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 0.083 (1003 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	NM_020911.2	MANE Select	c.1372-40802A>T		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.1372-40802A>T		intron	N/A	NP_001380826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.1372-40802A>T		intron	N/A	ENSP00000323194.4
	PLXNA4	ENST00000359827.7	TSL:5	c.1372-40802A>T		intron	N/A	ENSP00000352882.3

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12667 AN: 152070 Hom.: 997 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0834 AC: 12686 AN: 152188 Hom.: 1003 Cov.: 33 AF XY: 0.0926 AC XY: 6888 AN XY: 74396

African (AFR) AF: 0.0168 AC: 699 AN: 41560

American (AMR) AF: 0.136 AC: 2077 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1534 AN: 5164

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4808

European-Finnish (FIN) AF: 0.140 AC: 1484 AN: 10584

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4943 AN: 68000

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0490 Hom.: 60

Bravo AF: 0.0783

Asia WGS AF: 0.259 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.049
DANN	Benign	0.75
PhyloP100		-2.3
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: rs4731863; hg19: chr7-132023783;