7-132451945-C-T

Variant names:

• chr7-132451945-C-T
• rs1426492
• NM_020911.2:c.1371+37347G>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.1371+37347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,216 control chromosomes in the GnomAD database, including 43,413 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 0.70 (43413 hom., cov: 33)
• Consequence: PLXNA4 NM_020911.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA4	NM_020911.2	c.1371+37347G>A		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+37347G>A		intron_variant	Intron 3 of 31	5	NM_020911.2	ENSP00000323194.4
PLXNA4	ENST00000359827.7	c.1371+37347G>A		intron_variant	Intron 3 of 31	5		ENSP00000352882.3
PLXNA4	ENST00000423507.6	c.1371+37347G>A		intron_variant	Intron 3 of 3	2		ENSP00000392772.2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106611 AN: 152096 Hom.: 43421 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.700 AC: 106607 AN: 152216 Hom.: 43413 Cov.: 33 AF XY: 0.705 AC XY: 52490 AN XY: 74432

African (AFR) AF: 0.263 AC: 10919 AN: 41506

American (AMR) AF: 0.719 AC: 10995 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2843 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3669 AN: 5162

South Asian (SAS) AF: 0.804 AC: 3880 AN: 4824

European-Finnish (FIN) AF: 0.930 AC: 9866 AN: 10614

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61749 AN: 68024

Other (OTH) AF: 0.740 AC: 1565 AN: 2116

Alfa AF: 0.831 Hom.: 70773

Bravo AF: 0.665

Asia WGS AF: 0.722 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.38
PhyloP100		-0.52
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: rs1426492; hg19: chr7-132136704;