rs2056865

Variant names:

• chr7-116580478-G-A
• rs2056865
• ENST00000441991.2:n.188-6734C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-116580478-G-A
• chr7-116580478-G-T

Variant summary

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

The ENST00000441991.2(COMETT):​n.188-6734C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,984 control chromosomes in the GnomAD database, including 23,684 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 0.54 (23684 hom., cov: 32)
• Consequence: COMETT ENST00000441991.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMETT	NR_120506.2	n.204-6734C>T		intron_variant	Intron 2 of 4
COMETT	NR_165032.1	n.391-9248C>T		intron_variant	Intron 2 of 3
COMETT	NR_165033.1	n.391-6734C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMETT	ENST00000441991.2	n.188-6734C>T		intron_variant	Intron 1 of 2	3
COMETT	ENST00000450063.2	n.546-6734C>T		intron_variant	Intron 3 of 4	2
COMETT	ENST00000458082.2	n.367-6734C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81883 AN: 151866 Hom.: 23686 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.539 AC: 81889 AN: 151984 Hom.: 23684 Cov.: 32 AF XY: 0.536 AC XY: 39829 AN XY: 74292

African (AFR) AF: 0.349 AC: 14474 AN: 41424

American (AMR) AF: 0.461 AC: 7037 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1713 AN: 5162

South Asian (SAS) AF: 0.528 AC: 2541 AN: 4810

European-Finnish (FIN) AF: 0.684 AC: 7233 AN: 10576

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44839 AN: 67956

Other (OTH) AF: 0.538 AC: 1139 AN: 2116

Alfa AF: 0.524 Hom.: 2368

Bravo AF: 0.514

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs2056865; hg19: chr7-116220532;