12-94289428-G-A

Variant names:

• chr12-94289428-G-A
• rs4761470
• NM_005761.3:c.3880-5058G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

CEP83 Gene-Disease associations (from GenCC):

• nephronophthisis 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNC1	NM_005761.3	MANE Select	c.3880-5058G>A		intron	N/A	NP_005752.1
	PLXNC1	NR_037687.2		n.575-5058G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNC1	ENST00000258526.9	TSL:1 MANE Select	c.3880-5058G>A		intron	N/A	ENSP00000258526.4
	PLXNC1	ENST00000545312.1	TSL:1	c.97-5058G>A		intron	N/A	ENSP00000439225.1
	PLXNC1	ENST00000549217.5	TSL:1	n.1003-5058G>A		intron	N/A	ENSP00000446781.1

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

African (AFR) AF: 0.0876 AC: 3636 AN: 41514

American (AMR) AF: 0.194 AC: 2958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3472

East Asian (EAS) AF: 0.133 AC: 687 AN: 5178

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12967 AN: 67992

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.175 Hom.: 4771

Bravo AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.2
DANN	Benign	0.86
PhyloP100		0.35
Mutation Taster		=100/0	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: rs4761470; hg19: chr12-94683204;