rs42476

chr7-116656724-G-Achr7-116656724-G-Cchr7-116656724-G-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+7015C>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 0.921 in 152,114 control chromosomes in the GnomAD database, including 64,650 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 0.92 (64650 hom., cov: 32)
• Consequence: COMETT NR_165032.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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 (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COMETT	NR_165032.1	n.390+7015C>T		intron_variant, non_coding_transcript_variant
COMETT	NR_165033.1	n.390+7015C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMETT	ENST00000650435.1	n.92-1060C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.921 AC: 139992 AN: 151996 Hom.: 64592 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.921 AC: 140110 AN: 152114 Hom.: 64650 Cov.: 32 AF XY: 0.923 AC XY: 68607 AN XY: 74362

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.913

Alfa AF: 0.889 Hom.: 5058

Bravo AF: 0.926

Asia WGS AF: 0.941 AC: 3273 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	5.1
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs42476; hg19: chr7-116296778;