chr8-107252045-A-T

Variant names:

• chr8-107252045-A-T
• rs10088493
• NM_001146.5:c.1337-30T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146.5(ANGPT1):​c.1337-30T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,752 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.1337-30T>A		intron_variant	Intron 8 of 8	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.1334-30T>A		intron_variant	Intron 8 of 8		NP_001186788.1
ANGPT1	NM_001314051.2	c.737-30T>A		intron_variant	Intron 7 of 7		NP_001300980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.1337-30T>A		intron_variant	Intron 8 of 8	1	NM_001146.5	ENSP00000428340.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437752 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 713132

African (AFR) AF: 0.00 AC: 0 AN: 32740

American (AMR) AF: 0.00 AC: 0 AN: 42092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25234

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 83036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097584

Other (OTH) AF: 0.00 AC: 0 AN: 59340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs10088493; hg19: chr8-108264273;