rs2507800

Variant names:

• chr8-107250441-T-A
• rs2507800
• NM_001146.5:c.*1414A>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.*1414A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,918 control chromosomes in the GnomAD database, including 10,118 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 0.36 (10118 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ANGPT1 NM_001146.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 19 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.*1414A>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.*1414A>T		3_prime_UTR_variant	Exon 9 of 9		NP_001186788.1
ANGPT1	NM_001314051.2	c.*1414A>T		3_prime_UTR_variant	Exon 8 of 8		NP_001300980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.*1414A>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001146.5	ENSP00000428340.1
ANGPT1	ENST00000297450.7	c.*1414A>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000297450.3

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54551 AN: 151800 Hom.: 10108 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.374

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.359 AC: 54596 AN: 151918 Hom.: 10118 Cov.: 32 AF XY: 0.359 AC XY: 26651 AN XY: 74256

African (AFR) AF: 0.267 AC: 11074 AN: 41468

American (AMR) AF: 0.394 AC: 6015 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1222 AN: 3464

East Asian (EAS) AF: 0.402 AC: 2086 AN: 5184

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4812

European-Finnish (FIN) AF: 0.328 AC: 3459 AN: 10546

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27366 AN: 67882

Other (OTH) AF: 0.375 AC: 788 AN: 2104

Alfa AF: 0.375 Hom.: 1433

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.17
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: rs2507800; hg19: chr8-108262669;