rs17036508

Positions:

• chr1-11195977-T-C

Variant summary

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

The NM_021146.4(ANGPTL7):​c.*954T>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 0.0909 in 152,254 control chromosomes in the GnomAD database, including 1,025 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 0.091 (1025 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ANGPTL7 NM_021146.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

Genes affected

ANGPTL7 (HGNC:24078): (angiopoietin like 7) Enables identical protein binding activity. Involved in negative regulation of vasculature development involved in avascular cornea development in camera-type eye and regulation of extracellular matrix organization. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

MTOR (HGNC:3942): (mechanistic target of rapamycin kinase) The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]

MTOR (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL7	NM_021146.4	c.*954T>C		3_prime_UTR_variant	5/5	ENST00000376819.4	NP_066969.1
MTOR	NM_004958.4	c.4253+3281A>G		intron_variant		ENST00000361445.9	NP_004949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL7	ENST00000376819.4	c.*954T>C		3_prime_UTR_variant	5/5	1	NM_021146.4	ENSP00000366015.3
MTOR	ENST00000361445.9	c.4253+3281A>G		intron_variant		1	NM_004958.4	ENSP00000354558.4

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13803 AN: 152136 Hom.: 1015 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0922

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

GnomAD4 genome AF: 0.0909 AC: 13846 AN: 152254 Hom.: 1025 Cov.: 32 AF XY: 0.0952 AC XY: 7090 AN XY: 74454

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0238

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0358 Hom.: 167

Bravo AF: 0.0977

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17036508; hg19: chr1-11256034;