NM_003873.7:c.981+2887A>G

Variant names:

• chr10-33251141-T-C
• rs1888686
• NM_003873.7:c.981+2887A>G

Variant summary

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

The NM_003873.7(NRP1):​c.981+2887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,078 control chromosomes in the GnomAD database, including 5,753 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 0.26 (5753 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7	c.981+2887A>G		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.981+2887A>G		intron_variant	Intron 6 of 16	1	NM_003873.7	ENSP00000364001.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39916 AN: 151958 Hom.: 5744 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.263 AC: 39965 AN: 152078 Hom.: 5753 Cov.: 32 AF XY: 0.262 AC XY: 19496 AN XY: 74352

African (AFR) AF: 0.343 AC: 14233 AN: 41440

American (AMR) AF: 0.237 AC: 3618 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2774 AN: 5158

South Asian (SAS) AF: 0.237 AC: 1144 AN: 4822

European-Finnish (FIN) AF: 0.169 AC: 1793 AN: 10602

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14513 AN: 67986

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.242 Hom.: 614

Bravo AF: 0.275

Asia WGS AF: 0.370 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.49
PhyloP100		-2.0
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: rs1888686; hg19: chr10-33540069;