8-107252045-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146.5(ANGPT1):c.1337-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 1,589,926 control chromosomes in the GnomAD database, including 645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (323 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (322 hom.)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-107252045-A-G is Benign according to our data. Variant chr8-107252045-A-G is described in ClinVar as [Benign]. Clinvar id is 1247640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPT1	NM_001146.5	c.1337-30T>C		intron_variant		ENST00000517746.6
ANGPT1	NM_001199859.3	c.1334-30T>C		intron_variant
ANGPT1	NM_001314051.2	c.737-30T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPT1	ENST00000517746.6	c.1337-30T>C		intron_variant		1	NM_001146.5	P4

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5641 AN: 152102 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0117 AC: 2799 AN: 239940 Hom.: 133 AF XY: 0.00941 AC XY: 1221 AN XY: 129810

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.00773

Gnomad ASJ exome AF: 0.0365

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000246

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00793

GnomAD4 exome AF: 0.00495 AC: 7110 AN: 1437710 Hom.: 322 Cov.: 29 AF XY: 0.00456 AC XY: 3254 AN XY: 713114

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00865

Gnomad4 ASJ exome AF: 0.0335

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.0000759

Gnomad4 NFE exome AF: 0.000639

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0371 AC: 5648 AN: 152216 Hom.: 323 Cov.: 32 AF XY: 0.0350 AC XY: 2608 AN XY: 74432

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0228

Alfa AF: 0.0254 Hom.: 30

Bravo AF: 0.0417

Asia WGS AF: 0.0100 AC: 36 AN: 3478

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

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.2
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10088493; hg19: chr8-108264273;