NM_020911.2:c.5613T>C

Variant names:

• chr7-132130551-A-G
• rs2671103
• NM_020911.2:c.5613T>C

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.5613T>C​(p.Asp1871Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,613,950 control chromosomes in the GnomAD database, including 611,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.87 (58048 hom., cov: 32)
  • Exomes 𝑓: 0.87 (552990 hom.)
• Consequence: PLXNA4 NM_020911.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.921
• Publications: 15 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=-0.81).
• BP6: Variant 7-132130551-A-G is Benign according to our data. Variant chr7-132130551-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060996.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.921 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 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.5613T>C	p.Asp1871Asp	synonymous	Exon 32 of 32	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5613T>C	p.Asp1871Asp	synonymous	Exon 32 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.5613T>C	p.Asp1871Asp	synonymous	Exon 32 of 32	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5613T>C	p.Asp1871Asp	synonymous	Exon 32 of 32	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5613T>C	p.Asp1871Asp	synonymous	Exon 33 of 33	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132763 AN: 152104 Hom.: 58002 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.887

GnomAD2 exomes AF: 0.890 AC: 221851 AN: 249354 AF XY: 0.889

Gnomad AFR exome AF: 0.857

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.867

Gnomad EAS exome AF: 0.947

Gnomad FIN exome AF: 0.915

Gnomad NFE exome AF: 0.860

Gnomad OTH exome AF: 0.883

GnomAD4 exome AF: 0.869 AC: 1270764 AN: 1461728 Hom.: 552990 Cov.: 66 AF XY: 0.870 AC XY: 632642 AN XY: 727174

African (AFR) AF: 0.857 AC: 28703 AN: 33474

American (AMR) AF: 0.934 AC: 41780 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 22612 AN: 26134

East Asian (EAS) AF: 0.943 AC: 37433 AN: 39696

South Asian (SAS) AF: 0.918 AC: 79216 AN: 86258

European-Finnish (FIN) AF: 0.915 AC: 48862 AN: 53412

Middle Eastern (MID) AF: 0.873 AC: 5038 AN: 5768

European-Non Finnish (NFE) AF: 0.858 AC: 954486 AN: 1111870

Other (OTH) AF: 0.872 AC: 52634 AN: 60392

GnomAD4 genome AF: 0.873 AC: 132868 AN: 152222 Hom.: 58048 Cov.: 32 AF XY: 0.878 AC XY: 65326 AN XY: 74426

African (AFR) AF: 0.861 AC: 35753 AN: 41516

American (AMR) AF: 0.900 AC: 13777 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.946 AC: 4892 AN: 5172

South Asian (SAS) AF: 0.922 AC: 4442 AN: 4820

European-Finnish (FIN) AF: 0.920 AC: 9754 AN: 10606

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58284 AN: 68020

Other (OTH) AF: 0.886 AC: 1869 AN: 2110

Alfa AF: 0.865 Hom.: 168511

Bravo AF: 0.871

Asia WGS AF: 0.927 AC: 3221 AN: 3478

EpiCase AF: 0.856

EpiControl AF: 0.854

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	-0.81
CADD	Benign	0.23
DANN	Benign	0.54
PhyloP100		-0.92
Mutation Taster		=99/1	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: rs2671103; hg19: chr7-131815310; COSMIC: COSV108143060;