7-116671876-A-C

Variant names:

• chr7-116671876-A-C
• rs184953
• ENST00000450063.2:n.99-7835T>G

Variant summary

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

The ENST00000450063.2(COMETT):​n.99-7835T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,156 control chromosomes in the GnomAD database, including 56,484 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 0.86 (56484 hom., cov: 32)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	NR_165032.1		n.88-7835T>G		intron	N/A
	COMETT	NR_165033.1		n.88-7835T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	ENST00000450063.2	TSL:2	n.99-7835T>G		intron	N/A
	COMETT	ENST00000757593.1		n.99-7835T>G		intron	N/A
	COMETT	ENST00000757594.1		n.99-7835T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130898 AN: 152038 Hom.: 56438 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.861 AC: 131002 AN: 152156 Hom.: 56484 Cov.: 32 AF XY: 0.864 AC XY: 64278 AN XY: 74370

African (AFR) AF: 0.911 AC: 37866 AN: 41556

American (AMR) AF: 0.854 AC: 13067 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3076 AN: 3468

East Asian (EAS) AF: 0.892 AC: 4578 AN: 5132

South Asian (SAS) AF: 0.843 AC: 4067 AN: 4822

European-Finnish (FIN) AF: 0.858 AC: 9089 AN: 10592

Middle Eastern (MID) AF: 0.887 AC: 259 AN: 292

European-Non Finnish (NFE) AF: 0.830 AC: 56435 AN: 67968

Other (OTH) AF: 0.855 AC: 1807 AN: 2114

Alfa AF: 0.839 Hom.: 18676

Bravo AF: 0.865

Asia WGS AF: 0.848 AC: 2949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.67
PhyloP100		0.86
PromoterAI		0.097	Neutral

Splicing

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

Other links and lift over

dbSNP: rs184953; hg19: chr7-116311930;