chr7-132133091-T-C

Variant names:

• chr7-132133091-T-C
• rs75848889
• NM_020911.2:c.5547A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_020911.2(PLXNA4):​c.5547A>G​(p.Ala1849Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,040 control chromosomes in the GnomAD database, including 11,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.093 (961 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10522 hom.)
• Consequence: PLXNA4 NM_020911.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.95
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-132133091-T-C is Benign according to our data. Variant chr7-132133091-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059020.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 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.5547A>G	p.Ala1849Ala	synonymous	Exon 31 of 32	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5547A>G	p.Ala1849Ala	synonymous	Exon 31 of 32	NP_001380826.1	Q9HCM2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA4	ENST00000321063.9	TSL:5 MANE Select	c.5547A>G	p.Ala1849Ala	synonymous	Exon 31 of 32	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5547A>G	p.Ala1849Ala	synonymous	Exon 31 of 32	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5547A>G	p.Ala1849Ala	synonymous	Exon 32 of 33	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14194 AN: 152078 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.131 AC: 32707 AN: 249408 AF XY: 0.131

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.120

Gnomad FIN exome AF: 0.0359

Gnomad NFE exome AF: 0.0969

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.109 AC: 158886 AN: 1461844 Hom.: 10522 Cov.: 31 AF XY: 0.111 AC XY: 81059 AN XY: 727218

African (AFR) AF: 0.0392 AC: 1311 AN: 33478

American (AMR) AF: 0.277 AC: 12376 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2958 AN: 26134

East Asian (EAS) AF: 0.130 AC: 5154 AN: 39700

South Asian (SAS) AF: 0.208 AC: 17983 AN: 86254

European-Finnish (FIN) AF: 0.0373 AC: 1990 AN: 53418

Middle Eastern (MID) AF: 0.150 AC: 866 AN: 5766

European-Non Finnish (NFE) AF: 0.0983 AC: 109349 AN: 1111988

Other (OTH) AF: 0.114 AC: 6899 AN: 60390

GnomAD4 genome AF: 0.0933 AC: 14206 AN: 152196 Hom.: 961 Cov.: 32 AF XY: 0.0961 AC XY: 7153 AN XY: 74422

African (AFR) AF: 0.0400 AC: 1661 AN: 41524

American (AMR) AF: 0.216 AC: 3306 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3470

East Asian (EAS) AF: 0.118 AC: 612 AN: 5168

South Asian (SAS) AF: 0.200 AC: 965 AN: 4818

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10618

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6466 AN: 67992

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.0963 Hom.: 582

Bravo AF: 0.103

Asia WGS AF: 0.204 AC: 707 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PLXNA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.39
PhyloP100		-4.0
Mutation Taster		=96/4	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: rs75848889; hg19: chr7-131817850; COSMIC: COSV58128637;