rs11776085

Variant names:

• chr8-107482327-G-A
• rs11776085
• NM_001146.5:c.297+14935C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146.5(ANGPT1):​c.297+14935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,144 control chromosomes in the GnomAD database, including 242 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 0.053 (242 hom., cov: 32)
• Consequence: ANGPT1 NM_001146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 2 publications found

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]

ANGPT1 Gene-Disease associations (from GenCC):

• glaucoma

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• primary congenital glaucoma

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• angioedema, hereditary, 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.297+14935C>T		intron_variant	Intron 1 of 8	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.297+14935C>T		intron_variant	Intron 1 of 8		NP_001186788.1
ANGPT1	XM_047421699.1	c.297+14935C>T		intron_variant	Intron 1 of 6		XP_047277655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.297+14935C>T		intron_variant	Intron 1 of 8	1	NM_001146.5	ENSP00000428340.1
ANGPT1	ENST00000297450.7	c.297+14935C>T		intron_variant	Intron 1 of 8	1		ENSP00000297450.3
ANGPT1	ENST00000520033.1	c.-25+12236C>T		intron_variant	Intron 1 of 1	4		ENSP00000428908.1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8003 AN: 152026 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0460

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

GnomAD4 genome AF: 0.0526 AC: 7999 AN: 152144 Hom.: 242 Cov.: 32 AF XY: 0.0536 AC XY: 3988 AN XY: 74370

African (AFR) AF: 0.0619 AC: 2571 AN: 41520

American (AMR) AF: 0.0624 AC: 954 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 130 AN: 3472

East Asian (EAS) AF: 0.0925 AC: 477 AN: 5158

South Asian (SAS) AF: 0.110 AC: 530 AN: 4798

European-Finnish (FIN) AF: 0.0306 AC: 324 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2817 AN: 67998

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0473 Hom.: 23

Bravo AF: 0.0546

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11776085; hg19: chr8-108494555;