10-33178722-G-A

Variant names:

• chr10-33178722-G-A
• rs13324
• NM_003873.7:c.*1354C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	NM_003873.7	MANE Select	c.*1354C>T		3_prime_UTR	Exon 17 of 17	NP_003864.5
	NRP1	NR_045259.2		n.4208C>T		non_coding_transcript_exon	Exon 16 of 16
	NRP1	NM_001244972.2		c.*1354C>T		3_prime_UTR	Exon 17 of 17	NP_001231901.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP1	ENST00000374867.7	TSL:1 MANE Select	c.*1354C>T		3_prime_UTR	Exon 17 of 17	ENSP00000364001.2
	NRP1	ENST00000395995.5	TSL:1	c.*1354C>T		3_prime_UTR	Exon 16 of 16	ENSP00000379317.1
	NRP1	ENST00000374875.5	TSL:1	c.*1354C>T		3_prime_UTR	Exon 16 of 16	ENSP00000364009.1

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

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) AF: 0.236 AC: 65 AN: 276

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.531 AC: 22005 AN: 41426

American (AMR) AF: 0.260 AC: 3968 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3160 AN: 5162

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4820

European-Finnish (FIN) AF: 0.247 AC: 2612 AN: 10556

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19803 AN: 67956

Other (OTH) AF: 0.374 AC: 790 AN: 2112

Alfa AF: 0.312 Hom.: 3753

Bravo AF: 0.375

Asia WGS AF: 0.479 AC: 1661 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.34
PhyloP100		0.46
Mutation Taster		=98/2	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: rs13324; hg19: chr10-33467650;