rs13324

Positions:

• chr10-33178722-G-A
• chr10-33178722-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.*1354C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,248 control chromosomes in the GnomAD database, including 11,214 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 0.37 (11208 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6 hom.)
• Consequence: NRP1 NM_003873.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP1	NM_003873.7	c.*1354C>T		3_prime_UTR_variant	17/17	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.*1354C>T		3_prime_UTR_variant	17/17	1	NM_003873.7	ENSP00000364001	P3
NRP1	ENST00000374875.5	c.*1354C>T		3_prime_UTR_variant	16/16	1		ENSP00000364009
NRP1	ENST00000395995.5	c.*1354C>T		3_prime_UTR_variant	16/16	1		ENSP00000379317	A2
NRP1	ENST00000265371.8	c.*1354C>T		3_prime_UTR_variant	18/18	5		ENSP00000265371	P3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55494 AN: 151848 Hom.: 11197 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.232 AC: 65 AN: 280 Hom.: 6 Cov.: 0 AF XY: 0.247 AC XY: 42 AN XY: 170

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.365 AC: 55537 AN: 151968 Hom.: 11208 Cov.: 32 AF XY: 0.362 AC XY: 26895 AN XY: 74274

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.374

Alfa AF: 0.304 Hom.: 2974

Bravo AF: 0.375

Asia WGS AF: 0.479 AC: 1661 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.34

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: rs13324; hg19: chr10-33467650;