rs851007

Variant names:

• chr6-36096259-G-A
• rs851007
• NM_139012.3:c.762+193G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-36096259-G-A
• chr6-36096259-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.601 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.762+193G>A		intron	N/A	NP_620581.1	Q16539-1
	MAPK14	NM_001315.3		c.683-3929G>A		intron	N/A	NP_001306.1	L7RSM2
	MAPK14	NM_139014.3		c.762+193G>A		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.762+193G>A		intron	N/A	ENSP00000229794.4	Q16539-1
	MAPK14	ENST00000229795.8	TSL:1	c.683-3929G>A		intron	N/A	ENSP00000229795.3	Q16539-2
	MAPK14	ENST00000310795.8	TSL:1	c.762+193G>A		intron	N/A	ENSP00000308669.4	Q16539-4

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

African (AFR) AF: 0.198 AC: 2083 AN: 10542

American (AMR) AF: 0.418 AC: 4993 AN: 11936

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 5354 AN: 11654

East Asian (EAS) AF: 0.249 AC: 6793 AN: 27250

South Asian (SAS) AF: 0.612 AC: 17698 AN: 28910

European-Finnish (FIN) AF: 0.452 AC: 12248 AN: 27082

Middle Eastern (MID) AF: 0.564 AC: 1239 AN: 2196

European-Non Finnish (NFE) AF: 0.535 AC: 118414 AN: 221516

Other (OTH) AF: 0.483 AC: 10514 AN: 21778

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

African (AFR) AF: 0.201 AC: 8342 AN: 41492

American (AMR) AF: 0.448 AC: 6850 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5158

South Asian (SAS) AF: 0.619 AC: 2987 AN: 4822

European-Finnish (FIN) AF: 0.464 AC: 4913 AN: 10586

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36395 AN: 67940

Other (OTH) AF: 0.419 AC: 885 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		-0.0020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs851007; hg19: chr6-36064036;