Variant rs2229935 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.1266C>T(p.Tyr422Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,611,294 control chromosomes in the GnomAD database, including 67,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6438 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61456 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.379

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:

NRP1 (HGNC:):

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=-0.47).

BP6

Variant 10-33221735-G-A is Benign according to our data. Variant chr10-33221735-G-A is described in ClinVar as [Benign]. Clinvar id is 3060922.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.379 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 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.1266C>T	p.Tyr422Tyr	synonymous_variant	8/17	ENST00000374867.7	NP_003864.5	O14786-1Q68DN3Q59F20Q6AWA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7 linkuse as main transcript	c.1266C>T	p.Tyr422Tyr	synonymous_variant	8/17	1	NM_003873.7	ENSP00000364001.2		O14786-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42596

AN:

151930

Hom.:

6437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.322

AC:

81001

AN:

251332

Hom.:

14676

AF XY:

0.316

AC XY:

42950

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.639

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.281

AC:

409437

AN:

1459244

Hom.:

61456

Cov.:

AF XY:

0.282

AC XY:

204539

AN XY:

725966

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.626

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.280

AC:

42609

AN:

152050

Hom.:

6438

Cov.:

AF XY:

0.284

AC XY:

21120

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.266

Hom.:

3508

Bravo

AF:

0.287

Asia WGS

AF:

0.460

AC:

1598

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

-0.47

CADD

Benign

6.3

DANN

Benign

0.45

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