7-116663497-A-G

Variant names:

• chr7-116663497-A-G
• rs38833
• ENST00000450063.2:n.401+242T>C

Variant summary

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

The ENST00000450063.2(COMETT):​n.401+242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,144 control chromosomes in the GnomAD database, including 55,367 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 0.85 (55367 hom., cov: 31)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 1 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	NR_165032.1		n.390+242T>C		intron	N/A
	COMETT	NR_165033.1		n.390+242T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	ENST00000450063.2	TSL:2	n.401+242T>C		intron	N/A
	COMETT	ENST00000650435.1		n.91+242T>C		intron	N/A
	COMETT	ENST00000757593.1		n.401+242T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129656 AN: 152026 Hom.: 55329 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.853 AC: 129751 AN: 152144 Hom.: 55367 Cov.: 31 AF XY: 0.856 AC XY: 63688 AN XY: 74372

African (AFR) AF: 0.884 AC: 36707 AN: 41516

American (AMR) AF: 0.852 AC: 13029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3077 AN: 3470

East Asian (EAS) AF: 0.893 AC: 4620 AN: 5174

South Asian (SAS) AF: 0.823 AC: 3968 AN: 4820

European-Finnish (FIN) AF: 0.858 AC: 9060 AN: 10564

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56480 AN: 68002

Other (OTH) AF: 0.851 AC: 1793 AN: 2108

Alfa AF: 0.838 Hom.: 18528

Bravo AF: 0.856

Asia WGS AF: 0.832 AC: 2896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.78
PhyloP100		-0.22

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs38833;

hg19: chr7-116303551;