rs2068435

Positions:

• chr12-94267198-T-C

Variant summary

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

The NM_005761.3(PLXNC1):​c.3597+1973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,178 control chromosomes in the GnomAD database, including 1,839 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 (1839 hom., cov: 33)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNC1	NM_005761.3	c.3597+1973T>C		intron_variant		ENST00000258526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3597+1973T>C		intron_variant		1	NM_005761.3	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 152060 Hom.: 1839 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.156 AC: 23739 AN: 152178 Hom.: 1839 Cov.: 33 AF XY: 0.155 AC XY: 11524 AN XY: 74380

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.176

Alfa AF: 0.150 Hom.: 315

Bravo AF: 0.163

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.44

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: rs2068435; hg19: chr12-94660974;