NM_003873.7:c.430+1842T>C

Variant names:

• chr10-33268833-A-G
• rs1571781
• NM_003873.7:c.430+1842T>C

Variant summary

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

The NM_003873.7(NRP1):​c.430+1842T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,070 control chromosomes in the GnomAD database, including 31,692 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 (31692 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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.430+1842T>C		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.430+1842T>C		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.430+1842T>C		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.430+1842T>C		intron	N/A	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.430+1842T>C		intron	N/A	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.-113-4960T>C		intron	N/A	ENSP00000364009.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97206 AN: 151954 Hom.: 31668 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.640 AC: 97283 AN: 152070 Hom.: 31692 Cov.: 32 AF XY: 0.633 AC XY: 47067 AN XY: 74314

African (AFR) AF: 0.752 AC: 31217 AN: 41498

American (AMR) AF: 0.517 AC: 7891 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2064 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3291 AN: 5166

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4814

European-Finnish (FIN) AF: 0.590 AC: 6231 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41917 AN: 67982

Other (OTH) AF: 0.638 AC: 1347 AN: 2112

Alfa AF: 0.637 Hom.: 3837

Bravo AF: 0.641

Asia WGS AF: 0.591 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		-0.11
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: rs1571781; hg19: chr10-33557761;