rs12573218

Positions:

• chr10-33298805-C-T

Variant summary

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

The NM_003873.7(NRP1):​c.249-27949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,146 control chromosomes in the GnomAD database, including 1,049 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 0.11 (1049 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

Genes affected

NRP1 (HGNC:8004): (neuropilin 1) This gene encodes one of two neuropilins, which contain specific protein domains which allow them to participate in several different types of signaling pathways that control cell migration. Neuropilins contain a large N-terminal extracellular domain, made up of complement-binding, coagulation factor V/VIII, and meprin domains. These proteins also contains a short membrane-spanning domain and a small cytoplasmic domain. Neuropilins bind many ligands and various types of co-receptors; they affect cell survival, migration, and attraction. Some of the ligands and co-receptors bound by neuropilins are vascular endothelial growth factor (VEGF) and semaphorin family members. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Nov 2020]

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 (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP1	NM_003873.7	c.249-27949G>A		intron_variant		ENST00000374867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP1	ENST00000374867.7	c.249-27949G>A		intron_variant		1	NM_003873.7	P3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16136 AN: 152028 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.106 AC: 16125 AN: 152146 Hom.: 1049 Cov.: 32 AF XY: 0.106 AC XY: 7913 AN XY: 74374

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.105

Alfa AF: 0.124 Hom.: 641

Bravo AF: 0.103

Asia WGS AF: 0.119 AC: 414 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	2.4
DANN	Benign	0.75

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: rs12573218; hg19: chr10-33587733;