rs3794901

Variant names:

• chr18-50724684-G-A
• rs3794901
• NM_002747.4:c.854-1278G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002747.4(MAPK4):​c.854-1278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,224 control chromosomes in the GnomAD database, including 2,021 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 0.16 (2021 hom., cov: 33)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	NM_002747.4	MANE Select	c.854-1278G>A		intron	N/A	NP_002738.2	P31152
	MAPK4	NM_001292039.2		c.221-1278G>A		intron	N/A	NP_001278968.1	B4DEW2
	MAPK4	NM_001292040.2		c.692-4474G>A		intron	N/A	NP_001278969.1	K7ELV1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK4	ENST00000400384.7	TSL:1 MANE Select	c.854-1278G>A		intron	N/A	ENSP00000383234.1	P31152
	MAPK4	ENST00000592595.5	TSL:1	c.692-4474G>A		intron	N/A	ENSP00000466233.1	K7ELV1
	MAPK4	ENST00000903334.1		c.854-1278G>A		intron	N/A	ENSP00000573394.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23792 AN: 152106 Hom.: 2023 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.156 AC: 23791 AN: 152224 Hom.: 2021 Cov.: 33 AF XY: 0.158 AC XY: 11777 AN XY: 74432

African (AFR) AF: 0.101 AC: 4188 AN: 41540

American (AMR) AF: 0.147 AC: 2250 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1037 AN: 5174

South Asian (SAS) AF: 0.209 AC: 1011 AN: 4830

European-Finnish (FIN) AF: 0.202 AC: 2140 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12089 AN: 68010

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.174 Hom.: 9910

Bravo AF: 0.148

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		3.0
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: rs3794901; hg19: chr18-48251054;