rs7802124

Variant names:

• chr7-116565860-T-C
• rs7802124
• ENST00000650435.1:n.737-1692A>G

Variant summary

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

The NR_120506.2(COMETT):​n.621-1692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,004 control chromosomes in the GnomAD database, including 4,008 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 0.20 (4008 hom., cov: 31)
• Consequence: COMETT NR_120506.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMETT	NR_120506.2	n.621-1692A>G		intron_variant	Intron 4 of 4
COMETT	NR_165032.1	n.504-1692A>G		intron_variant	Intron 3 of 3
COMETT	NR_165033.1	n.808-1692A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMETT	ENST00000650435.1	n.737-1692A>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30953 AN: 151886 Hom.: 3996 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.00998

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.204 AC: 31009 AN: 152004 Hom.: 4008 Cov.: 31 AF XY: 0.198 AC XY: 14701 AN XY: 74324

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0919

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.202

Alfa AF: 0.177 Hom.: 593

Bravo AF: 0.213

Asia WGS AF: 0.0900 AC: 317 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7802124; hg19: chr7-116205914;