10-33218000-C-T

Variant names:

• chr10-33218000-C-T
• rs1360456
• NM_003873.7:c.1282+3719G>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.1282+3719G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,060 control chromosomes in the GnomAD database, including 6,410 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 0.28 (6410 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 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.1282+3719G>A		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.1282+3719G>A		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.1282+3719G>A		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.1282+3719G>A		intron	N/A	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.1282+3719G>A		intron	N/A	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374875.5	TSL:1	c.739+3719G>A		intron	N/A	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42510 AN: 151940 Hom.: 6409 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.280 AC: 42523 AN: 152060 Hom.: 6410 Cov.: 32 AF XY: 0.284 AC XY: 21076 AN XY: 74340

African (AFR) AF: 0.208 AC: 8631 AN: 41484

American (AMR) AF: 0.373 AC: 5701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3200 AN: 5162

South Asian (SAS) AF: 0.348 AC: 1672 AN: 4808

European-Finnish (FIN) AF: 0.289 AC: 3048 AN: 10556

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18361 AN: 67978

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.269 Hom.: 15683

Bravo AF: 0.286

Asia WGS AF: 0.460 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.83
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: rs1360456; hg19: chr10-33506928;