rs2247383

Positions:

• chr10-33200124-G-A
• chr10-33200124-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003873.7(NRP1):​c.1865-2415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,002 control chromosomes in the GnomAD database, including 14,360 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 0.43 (14360 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP1	NM_003873.7	c.1865-2415C>T		intron_variant		ENST00000374867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP1	ENST00000374867.7	c.1865-2415C>T		intron_variant		1	NM_003873.7	P3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65219 AN: 151884 Hom.: 14358 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.429 AC: 65249 AN: 152002 Hom.: 14360 Cov.: 32 AF XY: 0.430 AC XY: 31920 AN XY: 74302

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.457

Alfa AF: 0.427 Hom.: 2384

Bravo AF: 0.428

Asia WGS AF: 0.596 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.86

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: rs2247383; hg19: chr10-33489052;