10-33255001-T-G

Variant names:

• chr10-33255001-T-G
• rs1319013
• NM_003873.7:c.815-807A>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.815-807A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,000 control chromosomes in the GnomAD database, including 20,555 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 0.51 (20555 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 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.815-807A>C		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.815-807A>C		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.815-807A>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.815-807A>C		intron	N/A	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.815-807A>C		intron	N/A	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374875.5	TSL:1	c.272-807A>C		intron	N/A	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77943 AN: 151882 Hom.: 20540 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.513 AC: 78005 AN: 152000 Hom.: 20555 Cov.: 32 AF XY: 0.516 AC XY: 38376 AN XY: 74320

African (AFR) AF: 0.399 AC: 16553 AN: 41440

American (AMR) AF: 0.547 AC: 8365 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3619 AN: 5164

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4816

European-Finnish (FIN) AF: 0.610 AC: 6444 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37089 AN: 67952

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.526 Hom.: 54421

Bravo AF: 0.505

Asia WGS AF: 0.583 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		0.59
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: rs1319013; hg19: chr10-33543929;