6-36061522-C-T

Variant names:

• chr6-36061522-C-T
• rs851016
• NM_139012.3:c.305+2175C>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.305+2175C>T 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 152,262 control chromosomes in the GnomAD database, including 60,163 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 (60163 hom., cov: 32)
• Consequence: MAPK14 NM_139012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• 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=-0.92).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	NM_139012.3	MANE Select	c.305+2175C>T		intron	N/A	NP_620581.1	Q16539-1
	MAPK14	NM_001315.3		c.305+2175C>T		intron	N/A	NP_001306.1	L7RSM2
	MAPK14	NM_139014.3		c.305+2175C>T		intron	N/A	NP_620583.1	Q16539-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK14	ENST00000229794.9	TSL:1 MANE Select	c.305+2175C>T		intron	N/A	ENSP00000229794.4	Q16539-1
	MAPK14	ENST00000229795.8	TSL:1	c.305+2175C>T		intron	N/A	ENSP00000229795.3	Q16539-2
	MAPK14	ENST00000310795.8	TSL:1	c.305+2175C>T		intron	N/A	ENSP00000308669.4	Q16539-4

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135063 AN: 152144 Hom.: 60105 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.888 AC: 135181 AN: 152262 Hom.: 60163 Cov.: 32 AF XY: 0.889 AC XY: 66201 AN XY: 74438

African (AFR) AF: 0.924 AC: 38402 AN: 41548

American (AMR) AF: 0.907 AC: 13880 AN: 15302

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

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

South Asian (SAS) AF: 0.942 AC: 4551 AN: 4830

European-Finnish (FIN) AF: 0.844 AC: 8950 AN: 10600

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58208 AN: 67998

Other (OTH) AF: 0.882 AC: 1865 AN: 2114

Alfa AF: 0.869 Hom.: 7158

Bravo AF: 0.894

Asia WGS AF: 0.968 AC: 3362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		-0.071
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: rs851016; hg19: chr6-36029299;