8-107420551-G-T

Position:

• chr8-107420551-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146.5(ANGPT1):​c.298-73454C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,014 control chromosomes in the GnomAD database, including 2,092 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 0.16 (2092 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.298-73454C>A		intron_variant		ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.298-73454C>A		intron_variant			NP_001186788.1
ANGPT1	XM_047421699.1	c.298-73454C>A		intron_variant			XP_047277655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.298-73454C>A		intron_variant		1	NM_001146.5	ENSP00000428340	P4
ANGPT1	ENST00000297450.7	c.298-73454C>A		intron_variant		1		ENSP00000297450	A1
ANGPT1	ENST00000520033.1	c.-24-73454C>A		intron_variant		4		ENSP00000428908

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24628 AN: 151896 Hom.: 2091 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.162 AC: 24639 AN: 152014 Hom.: 2092 Cov.: 32 AF XY: 0.159 AC XY: 11807 AN XY: 74316

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0839 Hom.: 151

Bravo AF: 0.157

Asia WGS AF: 0.0550 AC: 190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1433189; hg19: chr8-108432779;