rs2804495

Positions:

• chr10-33323572-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP1	NM_003873.7	c.248+7136C>A		intron_variant		ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.248+7136C>A		intron_variant		1	NM_003873.7	ENSP00000364001.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90460 AN: 151750 Hom.: 29548 Cov.: 30

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.: 30 AF XY: 0.601 AC XY: 44566 AN XY: 74206

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.633

Alfa AF: 0.661 Hom.: 5915

Bravo AF: 0.579

Asia WGS AF: 0.558 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs2804495; hg19: chr10-33612500;