10-33251197-C-T

Variant names:

• chr10-33251197-C-T
• rs1888685
• NM_003873.7:c.981+2831G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003873.7(NRP1):​c.981+2831G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,020 control chromosomes in the GnomAD database, including 1,787 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 0.12 (1787 hom., cov: 32)
• Consequence: NRP1 NM_003873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.981+2831G>A		intron	N/A	NP_003864.5
	NRP1	NM_001244972.2		c.981+2831G>A		intron	N/A	NP_001231901.2
	NRP1	NM_001244973.2		c.981+2831G>A		intron	N/A	NP_001231902.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.981+2831G>A		intron	N/A	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.981+2831G>A		intron	N/A	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374875.5	TSL:1	c.438+2831G>A		intron	N/A	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18877 AN: 151902 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.124 AC: 18899 AN: 152020 Hom.: 1787 Cov.: 32 AF XY: 0.127 AC XY: 9441 AN XY: 74282

African (AFR) AF: 0.0344 AC: 1430 AN: 41512

American (AMR) AF: 0.136 AC: 2078 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3466

East Asian (EAS) AF: 0.514 AC: 2638 AN: 5134

South Asian (SAS) AF: 0.197 AC: 944 AN: 4792

European-Finnish (FIN) AF: 0.130 AC: 1376 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9419 AN: 67974

Other (OTH) AF: 0.134 AC: 281 AN: 2102

Alfa AF: 0.125 Hom.: 163

Bravo AF: 0.123

Asia WGS AF: 0.321 AC: 1113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.85
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1888685; hg19: chr10-33540125;