rs4324901

Positions:

• chr8-107289570-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.1038+4366C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,932 control chromosomes in the GnomAD database, including 7,303 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 0.28 (7303 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.1038+4366C>A		intron_variant		ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.1035+4366C>A		intron_variant			NP_001186788.1
ANGPT1	NM_001314051.2	c.438+4366C>A		intron_variant			NP_001300980.1
ANGPT1	XM_047421699.1	c.1038+4366C>A		intron_variant			XP_047277655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.1038+4366C>A		intron_variant		1	NM_001146.5	ENSP00000428340	P4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42694 AN: 151812 Hom.: 7301 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.281 AC: 42693 AN: 151932 Hom.: 7303 Cov.: 32 AF XY: 0.280 AC XY: 20758 AN XY: 74260

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.305

Alfa AF: 0.357 Hom.: 17625

Bravo AF: 0.280

Asia WGS AF: 0.295 AC: 1026 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4324901; hg19: chr8-108301798;