NM_020911.2:c.1504-24288C>A

Variant names:

• chr7-132265454-G-T
• rs717005
• NM_020911.2:c.1504-24288C>A

Variant summary

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

The NM_020911.2(PLXNA4):​c.1504-24288C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,136 control chromosomes in the GnomAD database, including 2,537 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 0.16 (2537 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 1 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]

ENSG00000225144 (HGNC:40452):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA4	NM_020911.2	c.1504-24288C>A		intron_variant	Intron 4 of 31	ENST00000321063.9	NP_065962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000321063.9	c.1504-24288C>A		intron_variant	Intron 4 of 31	5	NM_020911.2	ENSP00000323194.4
PLXNA4	ENST00000359827.7	c.1504-24288C>A		intron_variant	Intron 4 of 31	5		ENSP00000352882.3
ENSG00000225144	ENST00000445459.2	n.151-805G>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24146 AN: 152018 Hom.: 2525 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0608

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.159 AC: 24198 AN: 152136 Hom.: 2537 Cov.: 32 AF XY: 0.152 AC XY: 11340 AN XY: 74382

African (AFR) AF: 0.291 AC: 12060 AN: 41468

American (AMR) AF: 0.106 AC: 1624 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0540 AC: 260 AN: 4814

European-Finnish (FIN) AF: 0.0608 AC: 645 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8657 AN: 67998

Other (OTH) AF: 0.152 AC: 320 AN: 2112

Alfa AF: 0.144 Hom.: 382

Bravo AF: 0.169

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		0.015
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: rs717005; hg19: chr7-131950213;