Genetic Variant NRP1:p.Val179Val (chr10-33263767-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_003873.7(NRP1):c.537G>A(p.Val179Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,612,932 control chromosomes in the GnomAD database, including 28,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3776 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25137 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0240

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=-0.6).

BP6

Variant 10-33263767-C-T is Benign according to our data. Variant chr10-33263767-C-T is described in ClinVar as [Benign]. Clinvar id is 3059652.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.024 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7 link	c.537G>A	p.Val179Val	synonymous_variant	Exon 4 of 17	ENST00000374867.7	NP_003864.5	O14786-1Q68DN3Q59F20Q6AWA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7 link	c.537G>A	p.Val179Val	synonymous_variant	Exon 4 of 17	1	NM_003873.7	ENSP00000364001.2		O14786-1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32222

AN:

151816

Hom.:

3776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.201

AC:

50578

AN:

251416

Hom.:

6029

AF XY:

0.197

AC XY:

26739

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.472

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.177

AC:

259191

AN:

1460996

Hom.:

25137

Cov.:

AF XY:

0.177

AC XY:

128723

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.212

AC:

32259

AN:

151936

Hom.:

3776

Cov.:

AF XY:

0.214

AC XY:

15858

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.470

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.170

Hom.:

3554

Bravo

AF:

0.218

Asia WGS

AF:

0.332

AC:

1153

AN:

3478

EpiCase

AF:

0.164

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRP1-related disorder

Benign:1

Aug 01, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.60

CADD

Benign

0.78

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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