rs2070296

Variant names:

• chr10-33263767-C-A
• rs2070296
• NM_003873.7:c.537G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-33263767-C-A
• chr10-33263767-C-G
• chr10-33263767-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003873.7(NRP1):​c.537G>T​(p.Val179Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. V179V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NRP1 NM_003873.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.537G>T	p.Val179Val	synonymous	Exon 4 of 17	NP_003864.5
	NRP1	NM_001244972.2		c.537G>T	p.Val179Val	synonymous	Exon 4 of 17	NP_001231901.2
	NRP1	NM_001244973.2		c.537G>T	p.Val179Val	synonymous	Exon 4 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.537G>T	p.Val179Val	synonymous	Exon 4 of 17	ENSP00000364001.2	O14786-1
	NRP1	ENST00000395995.5	TSL:1	c.537G>T	p.Val179Val	synonymous	Exon 4 of 16	ENSP00000379317.1	E9PEP6
	NRP1	ENST00000374823.9	TSL:1	c.537G>T	p.Val179Val	synonymous	Exon 4 of 11	ENSP00000363956.5	Q5T7F0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461306 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727010

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111486

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		-0.024
PromoterAI		0.031	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2070296; hg19: chr10-33552695;