rs17714205

Variant names:

• chr6-36051559-C-T
• rs17714205
• NM_139012.3:c.117-1140C>T

Variant summary

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

The NM_139012.3(MAPK14):​c.117-1140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,230 control chromosomes in the GnomAD database, including 698 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 0.086 (698 hom., cov: 31)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 4 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 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.117-1140C>T		intron	N/A	NP_620581.1
	MAPK14	NM_001315.3		c.117-1140C>T		intron	N/A	NP_001306.1
	MAPK14	NM_139014.3		c.117-1140C>T		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.117-1140C>T		intron	N/A	ENSP00000229794.4
	MAPK14	ENST00000229795.8	TSL:1	c.117-1140C>T		intron	N/A	ENSP00000229795.3
	MAPK14	ENST00000310795.8	TSL:1	c.117-1140C>T		intron	N/A	ENSP00000308669.4

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13142 AN: 152116 Hom.: 698 Cov.: 31

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0863 AC: 13141 AN: 152230 Hom.: 698 Cov.: 31 AF XY: 0.0876 AC XY: 6522 AN XY: 74410

African (AFR) AF: 0.0275 AC: 1142 AN: 41530

American (AMR) AF: 0.0847 AC: 1297 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3472

East Asian (EAS) AF: 0.0532 AC: 276 AN: 5186

South Asian (SAS) AF: 0.102 AC: 490 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1467 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7455 AN: 68010

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.0955 Hom.: 121

Bravo AF: 0.0807

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.8
DANN	Benign	0.78
PhyloP100		0.11
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: rs17714205; hg19: chr6-36019336;