rs4268102

chr8-107396181-A-Cchr8-107396181-A-G

Variant summary

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

The NM_001146.5(ANGPT1):c.298-49084T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,996 control chromosomes in the GnomAD database, including 8,223 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 (8223 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPT1	NM_001146.5	c.298-49084T>G		intron_variant		ENST00000517746.6
ANGPT1	NM_001199859.3	c.298-49084T>G		intron_variant
ANGPT1	XM_047421699.1	c.298-49084T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPT1	ENST00000517746.6	c.298-49084T>G		intron_variant		1	NM_001146.5	P4
ANGPT1	ENST00000297450.7	c.298-49084T>G		intron_variant		1		A1
ANGPT1	ENST00000520033.1	c.-24-49084T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46440 AN: 151878 Hom.: 8207 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.306 AC: 46493 AN: 151996 Hom.: 8223 Cov.: 32 AF XY: 0.306 AC XY: 22764 AN XY: 74324

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.269

Alfa AF: 0.234 Hom.: 9234

Bravo AF: 0.321

Asia WGS AF: 0.399 AC: 1383 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.59
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4268102; hg19: chr8-108408409;