8-107275349-T-G

Variant names:

• chr8-107275349-T-G
• rs9297393
• NM_001146.5:c.1205+9333A>C

Variant summary

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

The NM_001146.5(ANGPT1):​c.1205+9333A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,032 control chromosomes in the GnomAD database, including 8,463 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 0.31 (8463 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPT1	NM_001146.5	MANE Select	c.1205+9333A>C		intron	N/A	NP_001137.2
	ANGPT1	NM_001199859.3		c.1202+9333A>C		intron	N/A	NP_001186788.1
	ANGPT1	NM_001314051.2		c.605+9333A>C		intron	N/A	NP_001300980.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPT1	ENST00000517746.6	TSL:1 MANE Select	c.1205+9333A>C		intron	N/A	ENSP00000428340.1
	ANGPT1	ENST00000297450.7	TSL:1	c.1202+9333A>C		intron	N/A	ENSP00000297450.3
	ANGPT1	ENST00000520734.5	TSL:2	c.605+9333A>C		intron	N/A	ENSP00000430750.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47656 AN: 151914 Hom.: 8455 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.314 AC: 47675 AN: 152032 Hom.: 8463 Cov.: 32 AF XY: 0.313 AC XY: 23221 AN XY: 74298

African (AFR) AF: 0.134 AC: 5557 AN: 41516

American (AMR) AF: 0.349 AC: 5320 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1758 AN: 5134

South Asian (SAS) AF: 0.358 AC: 1721 AN: 4806

European-Finnish (FIN) AF: 0.372 AC: 3924 AN: 10558

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27099 AN: 67970

Other (OTH) AF: 0.327 AC: 690 AN: 2110

Alfa AF: 0.371 Hom.: 24255

Bravo AF: 0.306

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.52
PhyloP100		0.74
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: rs9297393; hg19: chr8-108287577;