rs2073320

chr10-33264329-A-Gchr10-33264329-A-T

Variant summary

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

The NM_003873.7(NRP1):c.431-456T>C variant causes a intron change. The variant allele was found at a frequency of 0.641 in 152,140 control chromosomes in the GnomAD database, including 31,929 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 0.64 (31929 hom., cov: 33)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38

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=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP1	NM_003873.7	c.431-456T>C		intron_variant		ENST00000374867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP1	ENST00000374867.7	c.431-456T>C		intron_variant		1	NM_003873.7	P3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97515 AN: 152022 Hom.: 31902 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.641 AC: 97594 AN: 152140 Hom.: 31929 Cov.: 33 AF XY: 0.635 AC XY: 47223 AN XY: 74350

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.640

Alfa AF: 0.610 Hom.: 57523

Bravo AF: 0.643

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	15
Dann	Benign	0.83

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: rs2073320; hg19: chr10-33553257;