rs1954727

Positions:

• chr8-107250906-C-G
• chr8-107250906-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146.5(ANGPT1):​c.*949G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,542 control chromosomes in the GnomAD database, including 31,756 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 0.64 (31756 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ANGPT1 NM_001146.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT1	NM_001146.5	c.*949G>C		3_prime_UTR_variant	9/9	ENST00000517746.6	NP_001137.2
ANGPT1	NM_001199859.3	c.*949G>C		3_prime_UTR_variant	9/9		NP_001186788.1
ANGPT1	NM_001314051.2	c.*949G>C		3_prime_UTR_variant	8/8		NP_001300980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT1	ENST00000517746.6	c.*949G>C		3_prime_UTR_variant	9/9	1	NM_001146.5	ENSP00000428340.1
ANGPT1	ENST00000297450.7	c.*949G>C		3_prime_UTR_variant	9/9	1		ENSP00000297450.3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97194 AN: 151428 Hom.: 31729 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.642 AC: 97277 AN: 151542 Hom.: 31756 Cov.: 32 AF XY: 0.637 AC XY: 47190 AN XY: 74074

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.670

Alfa AF: 0.494 Hom.: 1052

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.61
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1954727; hg19: chr8-108263134; COSMIC: COSV52429773; COSMIC: COSV52429773;