10-33214251-C-A

Variant names:

• chr10-33214251-C-A
• rs2506155
• NM_003873.7:c.1283-534G>T

Variant summary

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

The NM_003873.7(NRP1):​c.1283-534G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,068 control chromosomes in the GnomAD database, including 1,451 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 0.14 (1451 hom., cov: 31)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7	c.1283-534G>T		intron_variant	Intron 8 of 16	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.1283-534G>T		intron_variant	Intron 8 of 16	1	NM_003873.7	ENSP00000364001.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20649 AN: 151950 Hom.: 1446 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.136 AC: 20666 AN: 152068 Hom.: 1451 Cov.: 31 AF XY: 0.135 AC XY: 10014 AN XY: 74330

African (AFR) AF: 0.111 AC: 4611 AN: 41472

American (AMR) AF: 0.104 AC: 1588 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.118 AC: 608 AN: 5164

South Asian (SAS) AF: 0.137 AC: 657 AN: 4794

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10590

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10482 AN: 67980

Other (OTH) AF: 0.159 AC: 336 AN: 2110

Alfa AF: 0.149 Hom.: 7269

Bravo AF: 0.130

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.076
DANN	Benign	0.39
PhyloP100		-2.7
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: rs2506155; hg19: chr10-33503179;