chr4-118702312-C-T

Variant names:

• chr4-118702312-C-T
• rs298998
• NM_020961.4:c.739-1623C>T

Variant summary

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

The NM_020961.4(METTL14):​c.739-1623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,310 control chromosomes in the GnomAD database, including 31,925 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 0.63 (31925 hom., cov: 28)
• Consequence: METTL14 NM_020961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

Genes affected

METTL14 (HGNC:29330): (methyltransferase 14, N6-adenosine-methyltransferase subunit) Enables mRNA binding activity. Contributes to mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity. Involved in mRNA metabolic process; negative regulation of hematopoietic progenitor cell differentiation; and positive regulation of translation. Located in nucleoplasm. Part of RNA N6-methyladenosine methyltransferase complex. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL14	NM_020961.4	c.739-1623C>T		intron_variant	Intron 8 of 10	ENST00000388822.10	NP_066012.1
METTL14	XM_047416029.1	c.739-574C>T		intron_variant	Intron 8 of 10		XP_047271985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL14	ENST00000388822.10	c.739-1623C>T		intron_variant	Intron 8 of 10	1	NM_020961.4	ENSP00000373474.3
METTL14	ENST00000506780.2	c.205-1623C>T		intron_variant	Intron 2 of 3	5		ENSP00000424111.2
METTL14	ENST00000628452.2	n.*470-1623C>T		intron_variant	Intron 8 of 10	5		ENSP00000486933.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95536 AN: 151194 Hom.: 31907 Cov.: 28

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.632 AC: 95595 AN: 151310 Hom.: 31925 Cov.: 28 AF XY: 0.638 AC XY: 47138 AN XY: 73916

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.608

Alfa AF: 0.686 Hom.: 6268

Bravo AF: 0.615

Asia WGS AF: 0.654 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.42

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: rs298998; hg19: chr4-119623467;