10-33201235-C-G

Position:

• chr10-33201235-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.5).
• 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/exons	MANE	UniProt
NRP1	NM_003873.7	c.1864+1656G>C		intron_variant		ENST00000374867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP1	ENST00000374867.7	c.1864+1656G>C		intron_variant		1	NM_003873.7	P3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70515 AN: 151852 Hom.: 16649 Cov.: 32

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: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.464 AC: 70576 AN: 151970 Hom.: 16667 Cov.: 32 AF XY: 0.464 AC XY: 34434 AN XY: 74248

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.482

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	11
DANN	Benign	0.74

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: rs1555319; hg19: chr10-33490163;