rs6944417

Positions:

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

Variant summary

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

The NR_165032.1(COMETT):​n.390+33605G>T 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 0.266 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 NR_165032.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMETT	NR_165032.1	n.390+33605G>T		intron_variant, non_coding_transcript_variant
COMETT	NR_165033.1	n.390+33605G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMETT	ENST00000650435.1	n.175+25447G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.237

Alfa AF: 0.0938 Hom.: 237

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6944417; hg19: chr7-116270188;