rs6944417

Variant names:

• chr7-116630134-C-A
• rs6944417
• ENST00000450063.2:n.402-29200G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-116630134-C-A
• chr7-116630134-C-G
• chr7-116630134-C-T

Variant summary

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

The ENST00000450063.2(COMETT):​n.402-29200G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,048 control chromosomes in the GnomAD database, including 9,033 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 0.27 (9033 hom., cov: 32)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 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+33605G>T		intron	N/A
	COMETT	NR_165033.1		n.390+33605G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	ENST00000450063.2	TSL:2	n.402-29200G>T		intron	N/A
	COMETT	ENST00000650435.1		n.175+25447G>T		intron	N/A
	COMETT	ENST00000757593.1		n.401+33605G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40347 AN: 151928 Hom.: 8996 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.266 AC: 40438 AN: 152048 Hom.: 9033 Cov.: 32 AF XY: 0.264 AC XY: 19643 AN XY: 74346

African (AFR) AF: 0.615 AC: 25468 AN: 41436

American (AMR) AF: 0.144 AC: 2208 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1155 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1594 AN: 10568

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7841 AN: 67986

Other (OTH) AF: 0.237 AC: 499 AN: 2108

Alfa AF: 0.0938 Hom.: 237

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs6944417; hg19: chr7-116270188;