rs1010826

Variant names:

• chr10-33184692-G-A
• rs1010826
• NM_003873.7:c.2431+936C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-33184692-G-A
• chr10-33184692-G-C

Variant summary

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

The ENST00000374867.7(NRP1):​c.2431+936C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,044 control chromosomes in the GnomAD database, including 6,996 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 0.29 (6996 hom., cov: 33)
• Consequence: NRP1 ENST00000374867.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374867.7. 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.2431+936C>T		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.2413+936C>T		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.2410+936C>T		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.2431+936C>T		intron	N/A	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.2431+936C>T		intron	N/A	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.1867+936C>T		intron	N/A	ENSP00000364009.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44670 AN: 151926 Hom.: 6989 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.294 AC: 44710 AN: 152044 Hom.: 6996 Cov.: 33 AF XY: 0.299 AC XY: 22211 AN XY: 74322

African (AFR) AF: 0.330 AC: 13683 AN: 41458

American (AMR) AF: 0.317 AC: 4848 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 925 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3324 AN: 5164

South Asian (SAS) AF: 0.366 AC: 1761 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2961 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16289 AN: 67970

Other (OTH) AF: 0.300 AC: 631 AN: 2106

Alfa AF: 0.268 Hom.: 742

Bravo AF: 0.301

Asia WGS AF: 0.468 AC: 1624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.056
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: rs1010826; hg19: chr10-33473620;