6-36070206-G-A

Variant names:

• chr6-36070206-G-A
• rs851011
• NM_139012.3:c.306-2667G>A

Variant summary

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

The NM_139012.3(MAPK14):​c.306-2667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,278 control chromosomes in the GnomAD database, including 60,242 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 0.89 (60242 hom., cov: 32)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 6 publications found

Genes affected

MAPK14 (HGNC:6876): (mitogen-activated protein kinase 14) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	NM_139012.3	MANE Select	c.306-2667G>A		intron	N/A	NP_620581.1
	MAPK14	NM_001315.3		c.306-2667G>A		intron	N/A	NP_001306.1
	MAPK14	NM_139014.3		c.306-2667G>A		intron	N/A	NP_620583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	ENST00000229794.9	TSL:1 MANE Select	c.306-2667G>A		intron	N/A	ENSP00000229794.4
	MAPK14	ENST00000229795.8	TSL:1	c.306-2667G>A		intron	N/A	ENSP00000229795.3
	MAPK14	ENST00000310795.8	TSL:1	c.306-2667G>A		intron	N/A	ENSP00000308669.4

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135153 AN: 152160 Hom.: 60184 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.904

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.888 AC: 135271 AN: 152278 Hom.: 60242 Cov.: 32 AF XY: 0.890 AC XY: 66262 AN XY: 74470

African (AFR) AF: 0.924 AC: 38411 AN: 41552

American (AMR) AF: 0.907 AC: 13871 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3130 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5172 AN: 5192

South Asian (SAS) AF: 0.943 AC: 4556 AN: 4832

European-Finnish (FIN) AF: 0.844 AC: 8952 AN: 10608

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.857 AC: 58290 AN: 68018

Other (OTH) AF: 0.884 AC: 1868 AN: 2112

Alfa AF: 0.871 Hom.: 7495

Bravo AF: 0.894

Asia WGS AF: 0.967 AC: 3359 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		0.31
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: rs851011; hg19: chr6-36037983;