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rs1048804

chr10-33180253-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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 (★).

Frequency

Genomes: 𝑓 0.33 ( 9940 hom., cov: 31)
Exomes 𝑓: 0.26 ( 55272 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.297 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
NRP1NM_003873.7 linkuse as main transcriptc.2595T>C p.Ser865= synonymous_variant 17/17 ENST00000374867.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRP1ENST00000374867.7 linkuse as main transcriptc.2595T>C p.Ser865= synonymous_variant 17/171 NM_003873.7 P3O14786-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.332
AC:
50432
AN:
151794
Hom.:
9929
Cov.:
31
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.:
35
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.332
AC:
50478
AN:
151912
Hom.:
9940
Cov.:
31
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

NRP1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This 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.

Other links and lift over

dbSNP: rs1048804; hg19: chr10-33469181; COSMIC: COSV55162454; API