rs4761470

chr12-94289428-G-Achr12-94289428-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005761.3(PLXNC1):c.3880-5058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,168 control chromosomes in the GnomAD database, including 2,095 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 0.16 (2095 hom., cov: 32)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

Genes affected

PLXNC1 (HGNC:9106): (plexin C1) This gene encodes a member of the plexin family. Plexins are transmembrane receptors for semaphorins, a large family of proteins that regulate axon guidance, cell motility and migration, and the immune response. The encoded protein and its ligand regulate melanocyte adhesion, and viral semaphorins may modulate the immune response by binding to this receptor. The encoded protein may be a tumor suppressor protein for melanoma. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jan 2011]

CEP83 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.3880-5058G>A		intron_variant		ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3880-5058G>A		intron_variant		1	NM_005761.3	P1
PLXNC1	ENST00000545312.1	c.97-5058G>A		intron_variant		1
PLXNC1	ENST00000549217.5	c.1003-5058G>A		intron_variant, NMD_transcript_variant		1
PLXNC1	ENST00000547057.5	c.1021-5058G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23832 AN: 152050 Hom.: 2090 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.157 AC: 23844 AN: 152168 Hom.: 2095 Cov.: 32 AF XY: 0.155 AC XY: 11536 AN XY: 74414

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.183

Alfa AF: 0.180 Hom.: 3367

Bravo AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	5.2
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs4761470; hg19: chr12-94683204;