chr10-33235753-C-G

Variant names:

• chr10-33235753-C-G
• rs1331314
• NM_003873.7:c.982-9464G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

NRP1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NRP1	NM_003873.7	c.982-9464G>C		intron_variant	Intron 6 of 16	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.982-9464G>C		intron_variant	Intron 6 of 16	1	NM_003873.7	ENSP00000364001.2

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

African (AFR) AF: 0.0972 AC: 4034 AN: 41520

American (AMR) AF: 0.130 AC: 1981 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2636 AN: 5168

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4828

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10600

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7737 AN: 68012

Other (OTH) AF: 0.134 AC: 284 AN: 2114

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
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1331314; hg19: chr10-33524681;