NM_003873.7:c.*835T>C

Variant names:

• chr10-33179241-A-G
• rs2506143
• NM_003873.7:c.*835T>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.*835T>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 152,586 control chromosomes in the GnomAD database, including 3,112 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 (3109 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: NRP1 NM_003873.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.*835T>C		3_prime_UTR	Exon 17 of 17	NP_003864.5
	NRP1	NM_001244972.2		c.*835T>C		3_prime_UTR	Exon 17 of 17	NP_001231901.2
	NRP1	NM_001244973.2		c.*835T>C		3_prime_UTR	Exon 17 of 17	NP_001231902.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.*835T>C		3_prime_UTR	Exon 17 of 17	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.*835T>C		3_prime_UTR	Exon 16 of 16	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374875.5	TSL:1	c.*835T>C		3_prime_UTR	Exon 16 of 16	ENSP00000364009.1	Q5JWQ6

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28986 AN: 152036 Hom.: 3100 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.141 AC: 61 AN: 432 Hom.: 3 Cov.: 0 AF XY: 0.140 AC XY: 36 AN XY: 258

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.141 AC: 58 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 1 AN: 12

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.191 AC: 29010 AN: 152154 Hom.: 3109 Cov.: 32 AF XY: 0.187 AC XY: 13886 AN XY: 74388

African (AFR) AF: 0.300 AC: 12462 AN: 41482

American (AMR) AF: 0.151 AC: 2314 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3470

East Asian (EAS) AF: 0.111 AC: 576 AN: 5176

South Asian (SAS) AF: 0.107 AC: 515 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1388 AN: 10600

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10571 AN: 68000

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.164 Hom.: 2827

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		2.1
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: rs2506143; hg19: chr10-33468169;