rs2073320

Variant names:

• chr10-33264329-A-G
• rs2073320
• NM_003873.7:c.431-456T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-33264329-A-G
• chr10-33264329-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003873.7(NRP1):​c.431-456T>C variant causes a intron change. The variant allele was found at a frequency of 0.641 in 152,140 control chromosomes in the GnomAD database, including 31,929 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 0.64 (31929 hom., cov: 33)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.431-456T>C		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.431-456T>C		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.431-456T>C		intron	N/A	NP_001231902.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.431-456T>C		intron	N/A	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.431-456T>C		intron	N/A	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374875.5	TSL:1	c.-113-456T>C		intron	N/A	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97515 AN: 152022 Hom.: 31902 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.641 AC: 97594 AN: 152140 Hom.: 31929 Cov.: 33 AF XY: 0.635 AC XY: 47223 AN XY: 74350

African (AFR) AF: 0.760 AC: 31557 AN: 41506

American (AMR) AF: 0.517 AC: 7904 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3297 AN: 5174

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4822

European-Finnish (FIN) AF: 0.591 AC: 6258 AN: 10580

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41810 AN: 67982

Other (OTH) AF: 0.640 AC: 1349 AN: 2108

Alfa AF: 0.618 Hom.: 124937

Bravo AF: 0.643

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		5.4
Mutation Taster		=99/1	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: rs2073320; hg19: chr10-33553257;