Variant rs1048804 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.2595T>C(p.Ser865=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,613,702 control chromosomes in the GnomAD database, including 65,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 9940 hom., cov: 31)

Exomes 𝑓: 0.26 ( 55272 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.297

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 10-33180253-A-G is Benign according to our data. Variant chr10-33180253-A-G is described in ClinVar as [Benign]. Clinvar id is 3059358.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.297 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 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.2595T>C	p.Ser865=	synonymous_variant	17/17	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.2595T>C	p.Ser865=	synonymous_variant	17/17	1	NM_003873.7	ENSP00000364001	P3	O14786-1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50432

AN:

151794

Hom.:

9929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.334

GnomAD3 exomes

AF:

0.285

AC:

71772

AN:

251420

Hom.:

12682

AF XY:

0.287

AC XY:

39003

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.641

Gnomad SAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.259

AC:

377979

AN:

1461790

Hom.:

55272

Cov.:

AF XY:

0.262

AC XY:

190227

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.544

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.656

Gnomad4 SAS exome

AF:

0.351

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.332

AC:

50478

AN:

151912

Hom.:

9940

Cov.:

AF XY:

0.329

AC XY:

24434

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.526

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.281

Hom.:

3100

Bravo

AF:

0.345

Asia WGS

AF:

0.488

AC:

1692

AN:

3478

EpiCase

AF:

0.244

EpiControl

AF:

0.246

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

Oct 21, 2019

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

-0.78

CADD

Benign

1.4

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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