chr11-28212221-A-G

Variant names:

• chr11-28212221-A-G
• rs11601602
• NM_001113528.2:c.407+1023A>G

Variant summary

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

The NM_001113528.2(METTL15):​c.407+1023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,908 control chromosomes in the GnomAD database, including 3,192 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 0.19 (3192 hom., cov: 31)
• Consequence: METTL15 NM_001113528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 7 publications found

Genes affected

METTL15 (HGNC:26606): (methyltransferase 15, mitochondrial 12S rRNA N4-cytidine) Predicted to enable rRNA (cytosine-N4-)-methyltransferase activity. Predicted to be involved in rRNA base methylation. Predicted to be located in mitochondrial matrix. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL15	NM_001113528.2	c.407+1023A>G		intron_variant	Intron 4 of 6	ENST00000407364.8	NP_001107000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000407364.8	c.407+1023A>G		intron_variant	Intron 4 of 6	5	NM_001113528.2	ENSP00000384369.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29042 AN: 151790 Hom.: 3195 Cov.: 31

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.191 AC: 29026 AN: 151908 Hom.: 3192 Cov.: 31 AF XY: 0.193 AC XY: 14337 AN XY: 74240

African (AFR) AF: 0.0985 AC: 4086 AN: 41466

American (AMR) AF: 0.175 AC: 2667 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3466

East Asian (EAS) AF: 0.0780 AC: 404 AN: 5180

South Asian (SAS) AF: 0.130 AC: 625 AN: 4822

European-Finnish (FIN) AF: 0.290 AC: 3051 AN: 10538

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16966 AN: 67848

Other (OTH) AF: 0.217 AC: 456 AN: 2106

Alfa AF: 0.220 Hom.: 7599

Bravo AF: 0.179

Asia WGS AF: 0.101 AC: 351 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11601602; hg19: chr11-28233768;