8-107399314-G-A

Variant names:

• chr8-107399314-G-A
• rs1283695
• NM_001146.5:c.298-52217C>T

Variant summary

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

The NM_001146.5(ANGPT1):​c.298-52217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,112 control chromosomes in the GnomAD database, including 47,239 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 0.79 (47239 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.298-52217C>T		intron_variant	Intron 1 of 8	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.298-52217C>T		intron_variant	Intron 1 of 8		NP_001186788.1
ANGPT1	XM_047421699.1	c.298-52217C>T		intron_variant	Intron 1 of 6		XP_047277655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.298-52217C>T		intron_variant	Intron 1 of 8	1	NM_001146.5	ENSP00000428340.1
ANGPT1	ENST00000297450.7	c.298-52217C>T		intron_variant	Intron 1 of 8	1		ENSP00000297450.3
ANGPT1	ENST00000520033.1	c.-24-52217C>T		intron_variant	Intron 1 of 1	4		ENSP00000428908.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119627 AN: 151994 Hom.: 47220 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.787 AC: 119696 AN: 152112 Hom.: 47239 Cov.: 32 AF XY: 0.788 AC XY: 58566 AN XY: 74338

African (AFR) AF: 0.738 AC: 30600 AN: 41480

American (AMR) AF: 0.776 AC: 11871 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4732 AN: 5174

South Asian (SAS) AF: 0.756 AC: 3644 AN: 4818

European-Finnish (FIN) AF: 0.811 AC: 8564 AN: 10566

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.808 AC: 54959 AN: 68000

Other (OTH) AF: 0.785 AC: 1654 AN: 2108

Alfa AF: 0.797 Hom.: 16829

Bravo AF: 0.782

Asia WGS AF: 0.787 AC: 2734 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.53
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1283695; hg19: chr8-108411542;