rs3730327

Variant names:

• chr6-36059365-A-G
• rs3730327
• NM_139012.3:c.305+18A>G

Variant summary

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

The NM_139012.3(MAPK14):​c.305+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,593,260 control chromosomes in the GnomAD database, including 11,534 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 0.16 (2697 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8837 hom.)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 18 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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.305+18A>G		intron	N/A	NP_620581.1
	MAPK14	NM_001315.3		c.305+18A>G		intron	N/A	NP_001306.1
	MAPK14	NM_139014.3		c.305+18A>G		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.305+18A>G		intron	N/A	ENSP00000229794.4
	MAPK14	ENST00000229795.8	TSL:1	c.305+18A>G		intron	N/A	ENSP00000229795.3
	MAPK14	ENST00000310795.8	TSL:1	c.305+18A>G		intron	N/A	ENSP00000308669.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24427 AN: 152030 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.112 AC: 28208 AN: 251098 AF XY: 0.109

Gnomad AFR exome AF: 0.326

Gnomad AMR exome AF: 0.0559

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.0755

Gnomad NFE exome AF: 0.0982

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.102 AC: 147288 AN: 1441112 Hom.: 8837 Cov.: 26 AF XY: 0.102 AC XY: 73162 AN XY: 718168

African (AFR) AF: 0.328 AC: 10745 AN: 32776

American (AMR) AF: 0.0611 AC: 2730 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4101 AN: 25986

East Asian (EAS) AF: 0.117 AC: 4608 AN: 39538

South Asian (SAS) AF: 0.105 AC: 8986 AN: 85812

European-Finnish (FIN) AF: 0.0807 AC: 4292 AN: 53212

Middle Eastern (MID) AF: 0.0878 AC: 503 AN: 5728

European-Non Finnish (NFE) AF: 0.0955 AC: 104484 AN: 1093744

Other (OTH) AF: 0.115 AC: 6839 AN: 59658

GnomAD4 genome AF: 0.161 AC: 24463 AN: 152148 Hom.: 2697 Cov.: 32 AF XY: 0.159 AC XY: 11813 AN XY: 74396

African (AFR) AF: 0.316 AC: 13121 AN: 41472

American (AMR) AF: 0.0986 AC: 1507 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3472

East Asian (EAS) AF: 0.128 AC: 661 AN: 5162

South Asian (SAS) AF: 0.102 AC: 492 AN: 4822

European-Finnish (FIN) AF: 0.0836 AC: 886 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6690 AN: 68014

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.118 Hom.: 879

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.014
DANN	Benign	0.69
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3730327; hg19: chr6-36027142; COSMIC: COSV57696043;