Genetic Variant ENST00000374823.9:c.*1405G>C (chr10-33201235-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000374823.9(NRP1):c.*1405G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,972 control chromosomes in the GnomAD database, including 16,668 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 0.46 ( 16667 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

NRP1
ENST00000374823.9 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

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:

ENSG00000238258 (HGNC:):

ENSG00000238258 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=-0.5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP1	NM_003873.7 link	c.1864+1656G>C		intron_variant	Intron 11 of 16	ENST00000374867.7	NP_003864.5	O14786-1Q68DN3Q59F20Q6AWA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7 link	c.1864+1656G>C		intron_variant	Intron 11 of 16	1	NM_003873.7	ENSP00000364001.2		O14786-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70515

AN:

151852

Hom.:

16649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.739

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.464

AC:

70576

AN:

151970

Hom.:

16667

Cov.:

AF XY:

0.464

AC XY:

34434

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.488

AC:

20243

AN:

41444

American (AMR)

AF:

0.449

AC:

6852

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1515

AN:

3464

East Asian (EAS)

AF:

0.738

AC:

3814

AN:

5166

South Asian (SAS)

AF:

0.506

AC:

2437

AN:

4818

European-Finnish (FIN)

AF:

0.438

AC:

4615

AN:

10528

Middle Eastern (MID)

AF:

0.486

AC:

142

AN:

292

European-Non Finnish (NFE)

AF:

0.435

AC:

29592

AN:

67968

Other (OTH)

AF:

0.482

AC:

1017

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1931

3863

5794

7726

9657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.296

Hom.:

737

Bravo

AF:

0.468

Asia WGS

AF:

0.614

AC:

2133

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.0030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over