7-132130556-G-A

Variant names:

• chr7-132130556-G-A
• rs150228337
• NM_020911.2:c.5608C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_020911.2(PLXNA4):​c.5608C>T​(p.His1870Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,614,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. H1870H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (20 hom.)
• Consequence: PLXNA4 NM_020911.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 8.09
• Publications: 11 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074129403).
• BP6: Variant 7-132130556-G-A is Benign according to our data. Variant chr7-132130556-G-A is described in ClinVar as Benign. ClinVar VariationId is 3041401.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 463 AD gene.

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.5608C>T	p.His1870Tyr	missense	Exon 32 of 32	NP_065962.1	Q9HCM2-1
	PLXNA4	NM_001393897.1		c.5608C>T	p.His1870Tyr	missense	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.5608C>T	p.His1870Tyr	missense	Exon 32 of 32	ENSP00000323194.4	Q9HCM2-1
	PLXNA4	ENST00000359827.7	TSL:5	c.5608C>T	p.His1870Tyr	missense	Exon 32 of 32	ENSP00000352882.3	Q9HCM2-1
	PLXNA4	ENST00000948949.1		c.5608C>T	p.His1870Tyr	missense	Exon 33 of 33	ENSP00000619008.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152130 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00372 AC: 928 AN: 249198 AF XY: 0.00410

Gnomad AFR exome AF: 0.000452

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00835

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00389

Gnomad OTH exome AF: 0.00611

GnomAD4 exome AF: 0.00345 AC: 5038 AN: 1461828 Hom.: 20 Cov.: 61 AF XY: 0.00362 AC XY: 2633 AN XY: 727222

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.00340 AC: 152 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00915 AC: 239 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00722 AC: 623 AN: 86256

European-Finnish (FIN) AF: 0.00118 AC: 63 AN: 53418

Middle Eastern (MID) AF: 0.0168 AC: 97 AN: 5766

European-Non Finnish (NFE) AF: 0.00321 AC: 3567 AN: 1111960

Other (OTH) AF: 0.00462 AC: 279 AN: 60394

GnomAD4 genome AF: 0.00304 AC: 463 AN: 152248 Hom.: 2 Cov.: 33 AF XY: 0.00306 AC XY: 228 AN XY: 74448

African (AFR) AF: 0.000867 AC: 36 AN: 41544

American (AMR) AF: 0.00497 AC: 76 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4822

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00344 AC: 234 AN: 68020

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00401 Hom.: 6

Bravo AF: 0.00331

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000743 AC: 3

ESP6500EA AF: 0.00516 AC: 43

ExAC AF: 0.00340 AC: 411

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00587

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
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.092
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.34	N
PhyloP100		8.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.16	B
Vest4		0.28
MVP		0.10
MPC		0.77
ClinPred		0.021	T
GERP RS		5.5
Varity_R		0.14
gMVP		0.12
Mutation Taster		=97/3	polymorphism

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: rs150228337; hg19: chr7-131815315; COSMIC: COSV58140480;