7-132412257-C-A

Variant names:

• chr7-132412257-C-A
• rs1000058
• NM_020911.2:c.1371+77035G>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.1371+77035G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,266 control chromosomes in the GnomAD database, including 404 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 0.065 (404 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 5 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	NM_020911.2	MANE Select	c.1371+77035G>T		intron	N/A	NP_065962.1
	PLXNA4	NM_001393897.1		c.1371+77035G>T		intron	N/A	NP_001380826.1
	PLXNA4	NM_001105543.2		c.1372-26962G>T		intron	N/A	NP_001099013.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.1371+77035G>T		intron	N/A	ENSP00000323194.4
	PLXNA4	ENST00000359827.7	TSL:5	c.1371+77035G>T		intron	N/A	ENSP00000352882.3
	PLXNA4	ENST00000948949.1		c.1371+77035G>T		intron	N/A	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9854 AN: 152148 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.0646 AC: 9837 AN: 152266 Hom.: 404 Cov.: 32 AF XY: 0.0673 AC XY: 5009 AN XY: 74460

African (AFR) AF: 0.0219 AC: 911 AN: 41568

American (AMR) AF: 0.0770 AC: 1178 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3466

East Asian (EAS) AF: 0.101 AC: 521 AN: 5184

South Asian (SAS) AF: 0.112 AC: 539 AN: 4820

European-Finnish (FIN) AF: 0.0993 AC: 1052 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5140 AN: 68012

Other (OTH) AF: 0.0814 AC: 172 AN: 2114

Alfa AF: 0.0736 Hom.: 553

Bravo AF: 0.0614

Asia WGS AF: 0.108 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-0.92
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: rs1000058; hg19: chr7-132097016;