rs2301573

Positions:

• chr3-129587076-T-C

Variant summary

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

The NM_015103.3(PLXND1):​c.1489-357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,158 control chromosomes in the GnomAD database, including 902 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 0.095 (902 hom., cov: 33)
• Consequence: PLXND1 NM_015103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

PLXND1 (HGNC:9107): (plexin D1) Enables protein domain specific binding activity. Predicted to be involved in several processes, including endothelial cell migration; nervous system development; and regulation of angiogenesis. Predicted to act upstream of or within several processes, including circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and positive regulation of protein binding activity. Located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXND1	NM_015103.3	c.1489-357A>G		intron_variant		ENST00000324093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXND1	ENST00000324093.9	c.1489-357A>G		intron_variant		1	NM_015103.3	P1
PLXND1	ENST00000505237.2	c.178-357A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14364 AN: 152040 Hom.: 896 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0928

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

GnomAD4 genome AF: 0.0945 AC: 14380 AN: 152158 Hom.: 902 Cov.: 33 AF XY: 0.0998 AC XY: 7424 AN XY: 74392

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0793 Hom.: 98

Bravo AF: 0.0962

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.67

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: rs2301573; hg19: chr3-129305919;