7-116645661-T-C

Position:

• chr7-116645661-T-C

Variant summary

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

The NR_165032.1(COMETT):​n.390+18078A>G variant causes a intron, non coding transcript 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 NR_165032.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COMETT	NR_165032.1	n.390+18078A>G		intron_variant, non_coding_transcript_variant
COMETT	NR_165033.1	n.390+18078A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMETT	ENST00000650435.1	n.175+9920A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.859

Alfa AF: 0.839 Hom.: 70552

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1002399; hg19: chr7-116285715;