rs42476

Variant names:

• chr7-116656724-G-A
• rs42476
• ENST00000450063.2:n.401+7015C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-116656724-G-A
• chr7-116656724-G-C
• chr7-116656724-G-T

Variant summary

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

The ENST00000450063.2(COMETT):​n.401+7015C>T variant causes a intron 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 ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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+7015C>T		intron	N/A
	COMETT	NR_165033.1		n.390+7015C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	ENST00000450063.2	TSL:2	n.401+7015C>T		intron	N/A
	COMETT	ENST00000650435.1		n.92-1060C>T		intron	N/A
	COMETT	ENST00000757593.1		n.401+7015C>T		intron	N/A

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

African (AFR) AF: 0.978 AC: 40630 AN: 41532

American (AMR) AF: 0.923 AC: 14079 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3242 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5159 AN: 5180

South Asian (SAS) AF: 0.920 AC: 4442 AN: 4828

European-Finnish (FIN) AF: 0.886 AC: 9400 AN: 10604

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60179 AN: 67930

Other (OTH) AF: 0.913 AC: 1926 AN: 2110

Alfa AF: 0.921 Hom.: 31721

Bravo AF: 0.926

Asia WGS AF: 0.941 AC: 3273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		0.058

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs42476;

hg19: chr7-116296778;