rs851007

chr6-36096259-G-Achr6-36096259-G-C

Variant summary

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

The NM_139012.3(MAPK14):c.762+193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 514,934 control chromosomes in the GnomAD database, including 61,743 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 0.42 (15016 hom., cov: 32)
  • Exomes 𝑓: 0.49 (46727 hom.)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK14	NM_139012.3	c.762+193G>A		intron_variant		ENST00000229794.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK14	ENST00000229794.9	c.762+193G>A		intron_variant		1	NM_139012.3	P3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63868 AN: 151952 Hom.: 15024 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.494 AC: 179336 AN: 362864 Hom.: 46727 Cov.: 3 AF XY: 0.504 AC XY: 95964 AN XY: 190454

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.420 AC: 63854 AN: 152070 Hom.: 15016 Cov.: 32 AF XY: 0.420 AC XY: 31227 AN XY: 74358

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.419

Alfa AF: 0.333 Hom.: 950

Bravo AF: 0.401

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.6
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs851007; hg19: chr6-36064036;