rs17295051

Variant names:

• chr8-107286044-T-C
• rs17295051
• NM_001146.5:c.1039-1196A>G

Variant summary

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

The NM_001146.5(ANGPT1):​c.1039-1196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,056 control chromosomes in the GnomAD database, including 2,237 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 0.17 (2237 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.1039-1196A>G		intron_variant	Intron 6 of 8	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.1036-1196A>G		intron_variant	Intron 6 of 8		NP_001186788.1
ANGPT1	NM_001314051.2	c.439-1196A>G		intron_variant	Intron 5 of 7		NP_001300980.1
ANGPT1	XM_047421699.1	c.1038+7892A>G		intron_variant	Intron 6 of 6		XP_047277655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.1039-1196A>G		intron_variant	Intron 6 of 8	1	NM_001146.5	ENSP00000428340.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25084 AN: 151940 Hom.: 2236 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.165 AC: 25095 AN: 152056 Hom.: 2237 Cov.: 32 AF XY: 0.167 AC XY: 12448 AN XY: 74332

African (AFR) AF: 0.112 AC: 4659 AN: 41490

American (AMR) AF: 0.172 AC: 2631 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 484 AN: 3464

East Asian (EAS) AF: 0.137 AC: 707 AN: 5160

South Asian (SAS) AF: 0.149 AC: 718 AN: 4814

European-Finnish (FIN) AF: 0.239 AC: 2526 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12931 AN: 67960

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.178 Hom.: 986

Bravo AF: 0.157

Asia WGS AF: 0.192 AC: 669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.041
DANN	Benign	0.50
PhyloP100		-2.8
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: rs17295051; hg19: chr8-108298272;