18-50582393-A-G

Position:

• chr18-50582393-A-G

Variant summary

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

The NM_002747.4(MAPK4):​c.-871+22150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,070 control chromosomes in the GnomAD database, including 37,519 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 0.70 (37519 hom., cov: 32)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.-871+22150A>G		intron_variant		ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.-871+22150A>G		intron_variant		1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000588540.1	c.-871+21634A>G		intron_variant		1		ENSP00000465661.1
MAPK4	ENST00000592595.5	c.-871+22150A>G		intron_variant		1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.-88+22150A>G		intron_variant		2		ENSP00000439231.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106402 AN: 151952 Hom.: 37512 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.700 AC: 106461 AN: 152070 Hom.: 37519 Cov.: 32 AF XY: 0.702 AC XY: 52164 AN XY: 74330

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.719

Alfa AF: 0.636 Hom.: 1912

Bravo AF: 0.698

Asia WGS AF: 0.691 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.81

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: rs2969972; hg19: chr18-48108763;