rs1331326

Variant names:

• chr10-33290962-C-T
• rs1331326
• NM_003873.7:c.249-20106G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003873.7(NRP1):​c.249-20106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,922 control chromosomes in the GnomAD database, including 29,220 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 0.62 (29220 hom., cov: 31)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7	c.249-20106G>A		intron_variant	Intron 2 of 16	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.249-20106G>A		intron_variant	Intron 2 of 16	1	NM_003873.7	ENSP00000364001.2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93518 AN: 151804 Hom.: 29208 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.616 AC: 93577 AN: 151922 Hom.: 29220 Cov.: 31 AF XY: 0.619 AC XY: 45958 AN XY: 74270

African (AFR) AF: 0.533 AC: 22071 AN: 41420

American (AMR) AF: 0.583 AC: 8892 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3533 AN: 5158

South Asian (SAS) AF: 0.666 AC: 3190 AN: 4792

European-Finnish (FIN) AF: 0.680 AC: 7192 AN: 10570

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44488 AN: 67946

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.640 Hom.: 132374

Bravo AF: 0.603

Asia WGS AF: 0.664 AC: 2309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.9
DANN	Benign	0.65
PhyloP100		1.3
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: rs1331326; hg19: chr10-33579890;