8-107420551-G-T

Variant names:

• chr8-107420551-G-T
• rs1433189
• NM_001146.5:c.298-73454C>A

Variant summary

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

The NM_001146.5(ANGPT1):​c.298-73454C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,014 control chromosomes in the GnomAD database, including 2,092 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 0.16 (2092 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 3 publications found

Genes affected

ANGPT1 (HGNC:484): (angiopoietin 1) This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Mutations in this gene are associated with hereditary angioedema. [provided by RefSeq, Aug 2020]

ANGPT1 Gene-Disease associations (from GenCC):

• glaucoma

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• primary congenital glaucoma

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• angioedema, hereditary, 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146.5. 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
	ANGPT1	NM_001146.5	MANE Select	c.298-73454C>A		intron	N/A	NP_001137.2
	ANGPT1	NM_001199859.3		c.298-73454C>A		intron	N/A	NP_001186788.1	Q15389-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPT1	ENST00000517746.6	TSL:1 MANE Select	c.298-73454C>A		intron	N/A	ENSP00000428340.1	Q15389-1
	ANGPT1	ENST00000297450.7	TSL:1	c.298-73454C>A		intron	N/A	ENSP00000297450.3	Q15389-2
	ANGPT1	ENST00000949598.1		c.298-73454C>A		intron	N/A	ENSP00000619657.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24628 AN: 151896 Hom.: 2091 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24639 AN: 152014 Hom.: 2092 Cov.: 32 AF XY: 0.159 AC XY: 11807 AN XY: 74316

African (AFR) AF: 0.167 AC: 6944 AN: 41468

American (AMR) AF: 0.105 AC: 1600 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5172

South Asian (SAS) AF: 0.0884 AC: 426 AN: 4818

European-Finnish (FIN) AF: 0.169 AC: 1787 AN: 10564

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.190 AC: 12896 AN: 67948

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.0880 Hom.: 167

Bravo AF: 0.157

Asia WGS AF: 0.0550 AC: 190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.63
PhyloP100		0.021
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1433189; hg19: chr8-108432779;