rs1331314

Positions:

• chr10-33235753-C-G

Variant summary

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

The NM_003873.7(NRP1):​c.982-9464G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,208 control chromosomes in the GnomAD database, including 1,628 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 0.13 (1628 hom., cov: 33)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP1	NM_003873.7	c.982-9464G>C		intron_variant		ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.982-9464G>C		intron_variant		1	NM_003873.7	ENSP00000364001	P3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19306 AN: 152090 Hom.: 1626 Cov.: 33

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.127 AC: 19312 AN: 152208 Hom.: 1628 Cov.: 33 AF XY: 0.130 AC XY: 9646 AN XY: 74410

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.134

Alfa AF: 0.118 Hom.: 132

Bravo AF: 0.130

Asia WGS AF: 0.330 AC: 1146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.54

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: rs1331314; hg19: chr10-33524681;