10-33236908-T-C

Variant names:

• chr10-33236908-T-C
• rs927099
• NM_003873.7:c.982-10619A>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.982-10619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,104 control chromosomes in the GnomAD database, including 30,089 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 0.61 (30089 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.982-10619A>G		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.982-10619A>G		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.982-10619A>G		intron	N/A	NP_001231902.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.982-10619A>G		intron	N/A	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.982-10619A>G		intron	N/A	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.439-10619A>G		intron	N/A	ENSP00000364009.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93187 AN: 151984 Hom.: 30033 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.613 AC: 93299 AN: 152104 Hom.: 30089 Cov.: 32 AF XY: 0.612 AC XY: 45535 AN XY: 74364

African (AFR) AF: 0.820 AC: 34061 AN: 41514

American (AMR) AF: 0.592 AC: 9041 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3472

East Asian (EAS) AF: 0.760 AC: 3935 AN: 5176

South Asian (SAS) AF: 0.517 AC: 2487 AN: 4814

European-Finnish (FIN) AF: 0.517 AC: 5482 AN: 10594

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34403 AN: 67954

Other (OTH) AF: 0.608 AC: 1281 AN: 2106

Alfa AF: 0.551 Hom.: 65789

Bravo AF: 0.632

Asia WGS AF: 0.654 AC: 2273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.32
PhyloP100		-1.4
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: rs927099; hg19: chr10-33525836;