12-94256549-A-G

Variant names:

• chr12-94256549-A-G
• rs2242499
• NM_005761.3:c.3087+1253A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005761.3(PLXNC1):​c.3087+1253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,676 control chromosomes in the GnomAD database, including 25,603 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 0.58 (25603 hom., cov: 29)
• Consequence: PLXNC1 NM_005761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNC1	NM_005761.3	c.3087+1253A>G		intron_variant	Intron 17 of 30	ENST00000258526.9	NP_005752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNC1	ENST00000258526.9	c.3087+1253A>G		intron_variant	Intron 17 of 30	1	NM_005761.3	ENSP00000258526.4
PLXNC1	ENST00000549217.5	n.210+1253A>G		intron_variant	Intron 3 of 14	1		ENSP00000446781.1
PLXNC1	ENST00000547057.5	c.228+1253A>G		intron_variant	Intron 2 of 15	2		ENSP00000446720.1
PLXNC1	ENST00000550080.5	c.228+1253A>G		intron_variant	Intron 2 of 2	4		ENSP00000447625.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87743 AN: 151558 Hom.: 25573 Cov.: 29

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.579 AC: 87830 AN: 151676 Hom.: 25603 Cov.: 29 AF XY: 0.578 AC XY: 42844 AN XY: 74118

African (AFR) AF: 0.619 AC: 25548 AN: 41292

American (AMR) AF: 0.595 AC: 9072 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1811 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2699 AN: 5156

South Asian (SAS) AF: 0.542 AC: 2596 AN: 4794

European-Finnish (FIN) AF: 0.593 AC: 6228 AN: 10504

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37995 AN: 67922

Other (OTH) AF: 0.574 AC: 1207 AN: 2102

Alfa AF: 0.564 Hom.: 40303

Bravo AF: 0.581

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		0.36
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: rs2242499; hg19: chr12-94650325;