rs7757672

Positions:

• chr6-36117548-G-A

Variant summary

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

The XM_047418234.1(MAPK14):​c.*1056G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,102 control chromosomes in the GnomAD database, including 4,952 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 0.23 (4952 hom., cov: 32)
• Consequence: MAPK14 XM_047418234.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK14	XM_047418234.1	c.*1056G>A		3_prime_UTR_variant	11/11		XP_047274190.1
MAPK14	XM_047418233.1	c.1027+1127G>A		intron_variant			XP_047274189.1
MAPK14	XM_047418235.1	c.1028-892G>A		intron_variant			XP_047274191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34449 AN: 151984 Hom.: 4952 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.226 AC: 34441 AN: 152102 Hom.: 4952 Cov.: 32 AF XY: 0.228 AC XY: 16967 AN XY: 74352

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0804

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.227

Alfa AF: 0.296 Hom.: 10320

Bravo AF: 0.211

Asia WGS AF: 0.189 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7757672; hg19: chr6-36085325;