dbSNP rs13324: NRP1:c.*1354C>T (chr10-33178722-G-A) – 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.*1354C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,248 control chromosomes in the GnomAD database, including 11,214 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 0.37 ( 11208 hom., cov: 32)

Exomes 𝑓: 0.23 ( 6 hom. )

Consequence

NRP1
NM_003873.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.458

Publications

9 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7 link	c.*1354C>T		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.*1354C>T	3_prime_UTR_variant	Exon 17 of 17	1	NM_003873.7	ENSP00000364001.2	O14786-1
NRP1	ENST00000395995.5 link	c.*1354C>T	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000379317.1	E9PEP6
NRP1	ENST00000374875.5 link	c.*1354C>T	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000364009.1	Q5JWQ6
NRP1	ENST00000265371.8 link	c.*1354C>T	3_prime_UTR_variant	Exon 18 of 18	5		ENSP00000265371.3	O14786-1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55494

AN:

151848

Hom.:

11197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.374

GnomAD4 exome

AF:

0.232

AC:

AN:

280

Hom.:

Cov.:

AF XY:

0.247

AC XY:

AN XY:

170

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.236

AC:

AN:

276

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.365

AC:

55537

AN:

151968

Hom.:

11208

Cov.:

AF XY:

0.362

AC XY:

26895

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.531

AC:

22005

AN:

41426

American (AMR)

AF:

0.260

AC:

3968

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3470

East Asian (EAS)

AF:

0.612

AC:

3160

AN:

5162

South Asian (SAS)

AF:

0.365

AC:

1759

AN:

4820

European-Finnish (FIN)

AF:

0.247

AC:

2612

AN:

10556

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19803

AN:

67956

Other (OTH)

AF:

0.374

AC:

790

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1733

3466

5198

6931

8664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.312

Hom.:

3753

Bravo

AF:

0.375

Asia WGS

AF:

0.479

AC:

1661

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.3

(source)

DANN

Benign

0.34

PhyloP100

0.46

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over