rs2506144

Positions:

• chr10-33179528-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.93).
• 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/exons	MANE	UniProt
NRP1	NM_003873.7	c.*548G>A		3_prime_UTR_variant	17/17	ENST00000374867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP1	ENST00000374867.7	c.*548G>A		3_prime_UTR_variant	17/17	1	NM_003873.7	P3
NRP1	ENST00000374875.5	c.*548G>A		3_prime_UTR_variant	16/16	1
NRP1	ENST00000395995.5	c.*548G>A		3_prime_UTR_variant	16/16	1		A2
NRP1	ENST00000265371.8	c.*548G>A		3_prime_UTR_variant	18/18	5		P3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29018 AN: 152044 Hom.: 3105 Cov.: 32

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.: 30 Cov.: 0 AF XY: 0.120 AC XY: 218 AN XY: 1822

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0807

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.0735

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.191 AC: 29042 AN: 152162 Hom.: 3114 Cov.: 32 AF XY: 0.187 AC XY: 13889 AN XY: 74394

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.199

Alfa AF: 0.163 Hom.: 4354

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
DANN	Benign	0.76

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: rs2506144; hg19: chr10-33468456;