chr18-50664141-C-G

Variant names:

• chr18-50664141-C-G
• rs55800528
• NM_002747.4:c.183C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002747.4(MAPK4):​c.183C>G​(p.His61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H61H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAPK4 NM_002747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 0 publications found

Genes affected

MAPK4 (HGNC:6878): (mitogen-activated protein kinase 4) Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3868485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002747.4. 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
	MAPK4	NM_002747.4	MANE Select	c.183C>G	p.His61Gln	missense	Exon 2 of 6	NP_002738.2	P31152
	MAPK4	NM_001292040.2		c.183C>G	p.His61Gln	missense	Exon 2 of 4	NP_001278969.1	K7ELV1
	MAPK4	NM_001292039.2		c.-87-50938C>G		intron	N/A	NP_001278968.1	B4DEW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	ENST00000400384.7	TSL:1 MANE Select	c.183C>G	p.His61Gln	missense	Exon 2 of 6	ENSP00000383234.1	P31152
	MAPK4	ENST00000588540.1	TSL:1	c.183C>G	p.His61Gln	missense	Exon 2 of 3	ENSP00000465661.1	K7EN18
	MAPK4	ENST00000592595.5	TSL:1	c.183C>G	p.His61Gln	missense	Exon 2 of 4	ENSP00000466233.1	K7ELV1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	0.031
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.25	N
PhyloP100		-2.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.34
Sift	Benign	0.054	T
Sift4G	Uncertain	0.052	T
Polyphen		0.49	P
Vest4		0.63
MutPred		0.67		Loss of methylation at R57 (P = 0.148)
MVP		0.57
MPC		1.6
ClinPred		0.74	D
GERP RS		-8.1
Varity_R		0.27
gMVP		0.65

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: rs55800528; hg19: chr18-48190511;