rs7214877

Variant names:

• chr17-2510914-G-A
• rs7214877
• NM_024086.4:c.-1+845C>T

Variant summary

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

The NM_024086.4(METTL16):​c.-1+845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,848 control chromosomes in the GnomAD database, including 28,035 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 0.57 (28035 hom., cov: 31)
• Consequence: METTL16 NM_024086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 2 publications found

Genes affected

METTL16 (HGNC:28484): (methyltransferase 16, RNA N6-adenosine) Enables RNA binding activity and RNA methyltransferase activity. Involved in RNA modification and regulation of mRNA metabolic process. Located in cytoplasm and nucleus. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL16	NM_024086.4	c.-1+845C>T		intron_variant	Intron 1 of 9	ENST00000263092.11	NP_076991.3
METTL16	XM_047436697.1	c.-281+845C>T		intron_variant	Intron 1 of 8		XP_047292653.1
METTL16	XR_007065448.1	n.130+845C>T		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11	c.-1+845C>T		intron_variant	Intron 1 of 9	1	NM_024086.4	ENSP00000263092.5

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86914 AN: 151730 Hom.: 28051 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.572 AC: 86915 AN: 151848 Hom.: 28035 Cov.: 31 AF XY: 0.570 AC XY: 42324 AN XY: 74210

African (AFR) AF: 0.273 AC: 11301 AN: 41332

American (AMR) AF: 0.547 AC: 8351 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2617 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2329 AN: 5164

South Asian (SAS) AF: 0.599 AC: 2879 AN: 4806

European-Finnish (FIN) AF: 0.671 AC: 7079 AN: 10546

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

European-Non Finnish (NFE) AF: 0.740 AC: 50294 AN: 67968

Other (OTH) AF: 0.616 AC: 1297 AN: 2106

Alfa AF: 0.689 Hom.: 158494

Bravo AF: 0.547

Asia WGS AF: 0.490 AC: 1708 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	4.6
DANN	Benign	0.60
PhyloP100		0.044
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7214877; hg19: chr17-2414208; COSMIC: COSV54015917;