rs2506140

Variant names:

• chr10-33178611-A-G
• rs2506140
• NM_003873.7:c.*1465T>C

Variant summary

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

The NM_003873.7(NRP1):​c.*1465T>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 0.191 in 152,178 control chromosomes in the GnomAD database, including 3,123 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 (3123 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: NRP1 NM_003873.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 9 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=-0.84).
• 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 rank	MANE	Protein	UniProt
NRP1	NM_003873.7	c.*1465T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000374867.7	NP_003864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP1	ENST00000374867.7	c.*1465T>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_003873.7	ENSP00000364001.2
NRP1	ENST00000395995.5	c.*1465T>C		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000379317.1
NRP1	ENST00000374875.5	c.*1465T>C		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000364009.1
NRP1	ENST00000265371.8	c.*1465T>C		3_prime_UTR_variant	Exon 18 of 18	5		ENSP00000265371.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29037 AN: 152060 Hom.: 3114 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.196

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.191 AC: 29061 AN: 152178 Hom.: 3123 Cov.: 33 AF XY: 0.187 AC XY: 13906 AN XY: 74412

African (AFR) AF: 0.301 AC: 12475 AN: 41494

American (AMR) AF: 0.152 AC: 2315 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.115 AC: 598 AN: 5180

South Asian (SAS) AF: 0.107 AC: 514 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1392 AN: 10604

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10583 AN: 68018

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.173 Hom.: 3276

Bravo AF: 0.197

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		1.3
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: rs2506140; hg19: chr10-33467539;