rs1370484

Variant names:

• chr18-50702972-G-T
• rs1370484
• NM_002747.4:c.547-12107G>T

Variant summary

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

The NM_002747.4(MAPK4):​c.547-12107G>T 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 152,186 control chromosomes in the GnomAD database, including 2,148 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 (2148 hom., cov: 32)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.547-12107G>T		intron_variant	Intron 2 of 5	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.547-12107G>T		intron_variant	Intron 2 of 5	1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000588540.1	c.547-1558G>T		intron_variant	Intron 2 of 2	1		ENSP00000465661.1
MAPK4	ENST00000592595.5	c.547-12107G>T		intron_variant	Intron 2 of 3	1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.-87-12107G>T		intron_variant	Intron 1 of 4	2		ENSP00000439231.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23721 AN: 152068 Hom.: 2143 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.156 AC: 23752 AN: 152186 Hom.: 2148 Cov.: 32 AF XY: 0.158 AC XY: 11790 AN XY: 74406

African (AFR) AF: 0.246 AC: 10197 AN: 41508

American (AMR) AF: 0.124 AC: 1894 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1140 AN: 5182

South Asian (SAS) AF: 0.140 AC: 675 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1783 AN: 10592

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7295 AN: 67996

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.146 Hom.: 564

Bravo AF: 0.159

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.6
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: rs1370484; hg19: chr18-48229342;