NM_002747.4:c.546+4927T>C

Variant names:

• chr18-50669431-T-C
• rs1893490
• NM_002747.4:c.546+4927T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000267713 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	NM_002747.4	MANE Select	c.546+4927T>C		intron	N/A	NP_002738.2
	MAPK4	NM_001292039.2		c.-87-45648T>C		intron	N/A	NP_001278968.1
	MAPK4	NM_001292040.2		c.546+4927T>C		intron	N/A	NP_001278969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	ENST00000400384.7	TSL:1 MANE Select	c.546+4927T>C		intron	N/A	ENSP00000383234.1
	MAPK4	ENST00000588540.1	TSL:1	c.546+4927T>C		intron	N/A	ENSP00000465661.1
	MAPK4	ENST00000592595.5	TSL:1	c.546+4927T>C		intron	N/A	ENSP00000466233.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.606 AC: 40 AN: 66

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.385 AC: 15982 AN: 41468

American (AMR) AF: 0.500 AC: 7643 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2210 AN: 5150

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4816

European-Finnish (FIN) AF: 0.500 AC: 5285 AN: 10580

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35539 AN: 67954

Other (OTH) AF: 0.512 AC: 1078 AN: 2104

Alfa AF: 0.512 Hom.: 85704

Bravo AF: 0.470

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.77
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: rs1893490; hg19: chr18-48195801;