dbSNP rs2506144: NRP1:c.*548G>A (chr10-33179528-C-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.*548G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 155,550 control chromosomes in the GnomAD database, including 3,144 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 0.19 ( 3114 hom., cov: 32)

Exomes 𝑓: 0.12 ( 30 hom. )

Consequence

NRP1
NM_003873.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

Publications

11 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7 link	c.*548G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000374867.7	NP_003864.5	O14786-1Q68DN3Q59F20Q6AWA9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRP1	ENST00000374867.7 link	c.*548G>A	3_prime_UTR_variant	Exon 17 of 17	1	NM_003873.7	ENSP00000364001.2	O14786-1
NRP1	ENST00000395995.5 link	c.*548G>A	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000379317.1	E9PEP6
NRP1	ENST00000374875.5 link	c.*548G>A	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000364009.1	Q5JWQ6
NRP1	ENST00000265371.8 link	c.*548G>A	3_prime_UTR_variant	Exon 18 of 18	5		ENSP00000265371.3	O14786-1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29018

AN:

152044

Hom.:

3105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.122

AC:

413

AN:

3388

Hom.:

Cov.:

AF XY:

0.120

AC XY:

218

AN XY:

1822

show subpopulations

African (AFR)

AF:

0.214

AC:

AN:

American (AMR)

AF:

0.0807

AC:

AN:

508

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

AN:

East Asian (EAS)

AF:

0.0455

AC:

AN:

South Asian (SAS)

AF:

0.0735

AC:

AN:

204

European-Finnish (FIN)

AF:

0.137

AC:

AN:

460

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.138

AC:

272

AN:

1974

Other (OTH)

AF:

0.112

AC:

AN:

116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.191

AC:

29042

AN:

152162

Hom.:

3114

Cov.:

AF XY:

0.187

AC XY:

13889

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.300

AC:

12457

AN:

41474

American (AMR)

AF:

0.151

AC:

2307

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

595

AN:

5184

South Asian (SAS)

AF:

0.106

AC:

510

AN:

4820

European-Finnish (FIN)

AF:

0.131

AC:

1393

AN:

10612

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10591

AN:

67992

Other (OTH)

AF:

0.199

AC:

420

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1198

2396

3594

4792

5990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.170

Hom.:

7502

Bravo

AF:

0.197

Asia WGS

AF:

0.140

AC:

487

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

(source)

DANN

Benign

0.76

PhyloP100

-0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over