7-132429858-A-G

Variant names:

• chr7-132429858-A-G
• rs2288975
• NM_020911.2:c.1371+59434T>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+59434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,186 control chromosomes in the GnomAD database, including 1,148 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 0.079 (1148 hom., cov: 32)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA4	NM_020911.2	c.1371+59434T>C		intron_variant	Intron 3 of 31	ENST00000321063.9	NP_065962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA4	ENST00000321063.9	c.1371+59434T>C		intron_variant	Intron 3 of 31	5	NM_020911.2	ENSP00000323194.4
PLXNA4	ENST00000359827.7	c.1371+59434T>C		intron_variant	Intron 3 of 31	5		ENSP00000352882.3
PLXNA4	ENST00000423507.6	c.1372-44563T>C		intron_variant	Intron 3 of 3	2		ENSP00000392772.2

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11956 AN: 152068 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.0629

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

GnomAD4 genome AF: 0.0787 AC: 11981 AN: 152186 Hom.: 1148 Cov.: 32 AF XY: 0.0786 AC XY: 5846 AN XY: 74416

African (AFR) AF: 0.210 AC: 8732 AN: 41490

American (AMR) AF: 0.0334 AC: 511 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1473 AN: 5162

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4820

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00773 AC: 526 AN: 68012

Other (OTH) AF: 0.0627 AC: 132 AN: 2106

Alfa AF: 0.0277 Hom.: 459

Bravo AF: 0.0866

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.062
DANN	Benign	0.41
PhyloP100		-1.2
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: rs2288975; hg19: chr7-132114617;