NM_020911.2:c.1371+80188A>C

Variant names:

• chr7-132409104-T-G
• rs2341823
• NM_020911.2:c.1371+80188A>C

Variant summary

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

The NM_020911.2(PLXNA4):​c.1371+80188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,154 control chromosomes in the GnomAD database, including 12,414 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 0.29 (12414 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 9 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]

ENSG00000297801 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 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.1371+80188A>C		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.1371+80188A>C		intron	N/A	NP_001380826.1
	PLXNA4	NM_001105543.2		c.1372-23809A>C		intron	N/A	NP_001099013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.1371+80188A>C		intron	N/A	ENSP00000323194.4
	ENSG00000297801	ENST00000751005.1		n.316A>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000297801	ENST00000751006.1		n.410A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43249 AN: 152036 Hom.: 12360 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.285 AC: 43370 AN: 152154 Hom.: 12414 Cov.: 32 AF XY: 0.280 AC XY: 20869 AN XY: 74404

African (AFR) AF: 0.730 AC: 30280 AN: 41476

American (AMR) AF: 0.276 AC: 4228 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1444 AN: 5172

South Asian (SAS) AF: 0.188 AC: 908 AN: 4822

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10618

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0729 AC: 4959 AN: 67984

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.213 Hom.: 1106

Bravo AF: 0.324

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		0.0020
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: rs2341823; hg19: chr7-132093863;