chr5-180288803-A-G

Position:

• chr5-180288803-A-G

Variant summary

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

The NM_002752.5(MAPK9):​c.-48+3045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,186 control chromosomes in the GnomAD database, including 7,590 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 0.31 (7590 hom., cov: 33)
• Consequence: MAPK9 NM_002752.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

Genes affected

MAPK9 (HGNC:6886): (mitogen-activated protein kinase 9) 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 targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK9	NM_002752.5	c.-48+3045T>C		intron_variant		ENST00000452135.7	NP_002743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK9	ENST00000452135.7	c.-48+3045T>C		intron_variant		5	NM_002752.5	ENSP00000394560.2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47608 AN: 152066 Hom.: 7579 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.313 AC: 47648 AN: 152186 Hom.: 7590 Cov.: 33 AF XY: 0.316 AC XY: 23492 AN XY: 74388

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.330

Alfa AF: 0.335 Hom.: 4710

Bravo AF: 0.303

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs745749; hg19: chr5-179715803; COSMIC: COSV58120087; COSMIC: COSV58120087;