8-107264365-G-GA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001146.5(ANGPT1):c.1206-15_1206-14insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,601,756 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (1 hom.)
• Consequence: ANGPT1 NM_001146.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-107264365-G-GA is Benign according to our data. Variant chr8-107264365-G-GA is described in ClinVar as [Benign]. Clinvar id is 1164156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPT1	NM_001146.5	c.1206-15_1206-14insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000517746.6
ANGPT1	NM_001199859.3	c.1203-15_1203-14insT		splice_polypyrimidine_tract_variant, intron_variant
ANGPT1	NM_001314051.2	c.606-15_606-14insT		splice_polypyrimidine_tract_variant, intron_variant
ANGPT1	XM_047421699.1	c.1039-15_1039-14insT		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPT1	ENST00000517746.6	c.1206-15_1206-14insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001146.5	P4

Frequencies

GnomAD3 genomes AF: 0.000317 AC: 48 AN: 151410 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000971

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000634

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000308 AC: 73 AN: 236958 Hom.: 0 AF XY: 0.000281 AC XY: 36 AN XY: 128278

Gnomad AFR exome AF: 0.0000633

Gnomad AMR exome AF: 0.000128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000579

Gnomad OTH exome AF: 0.000354

GnomAD4 exome AF: 0.000524 AC: 760 AN: 1450346 Hom.: 1 Cov.: 30 AF XY: 0.000538 AC XY: 388 AN XY: 721396

Gnomad4 AFR exome AF: 0.0000922

Gnomad4 AMR exome AF: 0.0000958

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000476

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000658

Gnomad4 OTH exome AF: 0.000301

GnomAD4 genome AF: 0.000317 AC: 48 AN: 151410 Hom.: 0 Cov.: 32 AF XY: 0.000271 AC XY: 20 AN XY: 73910

Gnomad4 AFR AF: 0.0000971

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000634

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000272

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs765718937; hg19: chr8-108276593;