rs1878553

Positions:

• chr18-2570156-C-T

Variant summary

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

The NM_022840.5(METTL4):​c.-439+993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,096 control chromosomes in the GnomAD database, including 4,844 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 0.24 (4844 hom., cov: 32)
• Consequence: METTL4 NM_022840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

Genes affected

METTL4 (HGNC:24726): (methyltransferase 4, N6-adenosine) Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in nucleic acid metabolic process; regulation of RNA metabolic process; and regulation of mitochondrial DNA replication. Located in cytosol; mitochondrial matrix; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL4	NM_022840.5	c.-439+993G>A		intron_variant		ENST00000574538.2	NP_073751.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL4	ENST00000574538.2	c.-439+993G>A		intron_variant		1	NM_022840.5	ENSP00000458290	P1
METTL4	ENST00000319888.10	c.-439+993G>A		intron_variant		5		ENSP00000320349
METTL4	ENST00000574676.1	c.-228+993G>A		intron_variant		2		ENSP00000461097
METTL4	ENST00000577166.5	c.-189+993G>A		intron_variant		4		ENSP00000458415

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37167 AN: 151978 Hom.: 4843 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.245 AC: 37195 AN: 152096 Hom.: 4844 Cov.: 32 AF XY: 0.241 AC XY: 17915 AN XY: 74362

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.225

Alfa AF: 0.234 Hom.: 5744

Bravo AF: 0.241

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1878553; hg19: chr18-2570155;