dbSNP rs2804495: NRP1:c.248+7136C>A (chr10-33323572-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003873.7(NRP1):c.248+7136C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,868 control chromosomes in the GnomAD database, including 29,551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 29551 hom., cov: 30)

Consequence

NRP1
NM_003873.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.464

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NRP1	NM_003873.7	MANE Select	c.248+7136C>A	intron	N/A	NP_003864.5
NRP1	NM_001244972.2		c.248+7136C>A	intron	N/A	NP_001231901.2
NRP1	NM_001244973.2		c.248+7136C>A	intron	N/A	NP_001231902.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRP1	ENST00000374867.7	TSL:1 MANE Select	c.248+7136C>A	intron	N/A	ENSP00000364001.2	O14786-1
NRP1	ENST00000395995.5	TSL:1	c.248+7136C>A	intron	N/A	ENSP00000379317.1	E9PEP6
NRP1	ENST00000374875.5	TSL:1	c.-114+7136C>A	intron	N/A	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90460

AN:

151750

Hom.:

29548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.596

AC:

90472

AN:

151868

Hom.:

29551

Cov.:

AF XY:

0.601

AC XY:

44566

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.305

AC:

12643

AN:

41406

American (AMR)

AF:

0.704

AC:

10754

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.777

AC:

2696

AN:

3468

East Asian (EAS)

AF:

0.613

AC:

3149

AN:

5136

South Asian (SAS)

AF:

0.594

AC:

2854

AN:

4802

European-Finnish (FIN)

AF:

0.734

AC:

7727

AN:

10528

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.715

AC:

48587

AN:

67952

Other (OTH)

AF:

0.633

AC:

1332

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.678

Hom.:

50299

Bravo

AF:

0.579

Asia WGS

AF:

0.558

AC:

1942

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.48

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over