rs437

Variant names:

• chr7-116656842-C-T
• rs437
• ENST00000450063.2:n.401+6897G>A

Variant summary

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

The ENST00000450063.2(COMETT):​n.401+6897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,982 control chromosomes in the GnomAD database, including 28,904 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 0.58 (28904 hom., cov: 33)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMETT	NR_165032.1	n.390+6897G>A		intron_variant	Intron 2 of 3
COMETT	NR_165033.1	n.390+6897G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMETT	ENST00000450063.2	n.401+6897G>A		intron_variant	Intron 2 of 4	2
COMETT	ENST00000650435.1	n.92-1178G>A		intron_variant	Intron 1 of 5
COMETT	ENST00000757593.1	n.401+6897G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88493 AN: 151864 Hom.: 28907 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.582 AC: 88503 AN: 151982 Hom.: 28904 Cov.: 33 AF XY: 0.588 AC XY: 43703 AN XY: 74318

African (AFR) AF: 0.258 AC: 10702 AN: 41444

American (AMR) AF: 0.704 AC: 10743 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2706 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3560 AN: 5160

South Asian (SAS) AF: 0.589 AC: 2837 AN: 4820

European-Finnish (FIN) AF: 0.704 AC: 7457 AN: 10592

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48384 AN: 67926

Other (OTH) AF: 0.616 AC: 1298 AN: 2108

Alfa AF: 0.669 Hom.: 106201

Bravo AF: 0.571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.41
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs437; hg19: chr7-116296896; COSMIC: COSV70617798;