chr10-33240100-G-T

Variant names:

• chr10-33240100-G-T
• rs2269091
• NM_003873.7:c.982-13811C>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.982-13811C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,030 control chromosomes in the GnomAD database, including 4,090 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 0.23 (4090 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 6 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 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.982-13811C>A		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.982-13811C>A		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.982-13811C>A		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.982-13811C>A		intron	N/A	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.982-13811C>A		intron	N/A	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.439-13811C>A		intron	N/A	ENSP00000364009.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34485 AN: 151912 Hom.: 4089 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.227 AC: 34505 AN: 152030 Hom.: 4090 Cov.: 32 AF XY: 0.227 AC XY: 16858 AN XY: 74314

African (AFR) AF: 0.279 AC: 11555 AN: 41458

American (AMR) AF: 0.291 AC: 4443 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3466

East Asian (EAS) AF: 0.152 AC: 789 AN: 5174

South Asian (SAS) AF: 0.144 AC: 693 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2229 AN: 10578

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13321 AN: 67952

Other (OTH) AF: 0.223 AC: 469 AN: 2102

Alfa AF: 0.198 Hom.: 5378

Bravo AF: 0.237

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.34
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: rs2269091; hg19: chr10-33529028;