Variant rs3750733 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003873.7(NRP1):c.60C>T(p.Gly20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,542,044 control chromosomes in the GnomAD database, including 7,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 621 hom., cov: 31)

Exomes 𝑓: 0.095 ( 7157 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.58

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-33334323-G-A is Benign according to our data. Variant chr10-33334323-G-A is described in ClinVar as [Benign]. Clinvar id is 3057002.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP1	NM_003873.7 linkuse as main transcript	c.60C>T	p.Gly20=	synonymous_variant	1/17	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7 linkuse as main transcript	c.60C>T	p.Gly20=	synonymous_variant	1/17	1	NM_003873.7	ENSP00000364001	P3	O14786-1

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12145

AN:

152110

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0837

Gnomad OTH

AF:

0.0808

GnomAD3 exomes

AF:

0.109

AC:

15177

AN:

139364

Hom.:

1100

AF XY:

0.112

AC XY:

8444

AN XY:

75412

show subpopulations

Gnomad AFR exome

AF:

0.0430

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.0586

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0832

Gnomad OTH exome

AF:

0.0927

GnomAD4 exome

AF:

0.0955

AC:

132685

AN:

1389816

Hom.:

7157

Cov.:

AF XY:

0.0974

AC XY:

66788

AN XY:

685678

show subpopulations

Gnomad4 AFR exome

AF:

0.0430

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0554

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.0668

Gnomad4 NFE exome

AF:

0.0895

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0799

AC:

12159

AN:

152228

Hom.:

621

Cov.:

AF XY:

0.0819

AC XY:

6095

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0477

Gnomad4 AMR

AF:

0.0907

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.0676

Gnomad4 NFE

AF:

0.0836

Gnomad4 OTH

AF:

0.0818

Alfa

AF:

0.0832

Hom.:

334

Bravo

AF:

0.0778

Asia WGS

AF:

0.214

AC:

745

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over