7-116645661-T-C

Variant names:

• chr7-116645661-T-C
• rs1002399
• ENST00000450063.2:n.401+18078A>G

Variant summary

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

The ENST00000450063.2(COMETT):​n.401+18078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,190 control chromosomes in the GnomAD database, including 57,105 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 0.87 (57105 hom., cov: 31)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 5 publications found

Genes affected

COMETT (HGNC:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMETT	NR_165032.1	n.390+18078A>G		intron_variant	Intron 2 of 3
COMETT	NR_165033.1	n.390+18078A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMETT	ENST00000450063.2	n.401+18078A>G		intron_variant	Intron 2 of 4	2
COMETT	ENST00000650435.1	n.175+9920A>G		intron_variant	Intron 2 of 5
COMETT	ENST00000757593.1	n.401+18078A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131566 AN: 152072 Hom.: 57045 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.865 AC: 131686 AN: 152190 Hom.: 57105 Cov.: 31 AF XY: 0.868 AC XY: 64611 AN XY: 74408

African (AFR) AF: 0.929 AC: 38567 AN: 41524

American (AMR) AF: 0.855 AC: 13062 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3070 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4617 AN: 5172

South Asian (SAS) AF: 0.829 AC: 3990 AN: 4814

European-Finnish (FIN) AF: 0.858 AC: 9100 AN: 10606

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56448 AN: 68000

Other (OTH) AF: 0.859 AC: 1814 AN: 2112

Alfa AF: 0.843 Hom.: 161298

Bravo AF: 0.869

Asia WGS AF: 0.838 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.088
DANN	Benign	0.25
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs1002399; hg19: chr7-116285715;