rs1893490

Positions:

• chr18-50669431-T-C

Variant summary

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

The NM_002747.4(MAPK4):​c.546+4927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,114 control chromosomes in the GnomAD database, including 17,704 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 0.48 (17691 hom., cov: 32)
  • Exomes 𝑓: 0.58 (13 hom.)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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]

MAPK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.546+4927T>C		intron_variant		ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.546+4927T>C		intron_variant		1	NM_002747.4	ENSP00000383234.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72747 AN: 151918 Hom.: 17684 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.577 AC: 45 AN: 78 Hom.: 13 Cov.: 0 AF XY: 0.589 AC XY: 33 AN XY: 56

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.479 AC: 72779 AN: 152036 Hom.: 17691 Cov.: 32 AF XY: 0.479 AC XY: 35609 AN XY: 74310

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.512

Alfa AF: 0.520 Hom.: 40352

Bravo AF: 0.470

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.32

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: rs1893490; hg19: chr18-48195801;