chr8-107463628-C-T

Variant names:

• chr8-107463628-C-T
• rs1283726
• NM_001146.5:c.297+33634G>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.297+33634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,088 control chromosomes in the GnomAD database, including 65,134 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 0.92 (65134 hom., cov: 31)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.297+33634G>A		intron_variant	Intron 1 of 8	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.297+33634G>A		intron_variant	Intron 1 of 8		NP_001186788.1
ANGPT1	XM_047421699.1	c.297+33634G>A		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.297+33634G>A		intron_variant	Intron 1 of 8	1	NM_001146.5	ENSP00000428340.1
ANGPT1	ENST00000297450.7	c.297+33634G>A		intron_variant	Intron 1 of 8	1		ENSP00000297450.3
ANGPT1	ENST00000520033.1	c.-25+30935G>A		intron_variant	Intron 1 of 1	4		ENSP00000428908.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140463 AN: 151970 Hom.: 65074 Cov.: 31

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.924 AC: 140582 AN: 152088 Hom.: 65134 Cov.: 31 AF XY: 0.924 AC XY: 68705 AN XY: 74336

African (AFR) AF: 0.981 AC: 40714 AN: 41520

American (AMR) AF: 0.934 AC: 14241 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3050 AN: 3466

East Asian (EAS) AF: 0.978 AC: 5045 AN: 5158

South Asian (SAS) AF: 0.895 AC: 4314 AN: 4822

European-Finnish (FIN) AF: 0.892 AC: 9430 AN: 10576

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60677 AN: 67982

Other (OTH) AF: 0.937 AC: 1980 AN: 2114

Alfa AF: 0.899 Hom.: 45499

Bravo AF: 0.931

Asia WGS AF: 0.951 AC: 3301 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.85
PhyloP100		-1.8
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: rs1283726; hg19: chr8-108475856;