chr18-50674143-C-T

Position:

• chr18-50674143-C-T

Variant summary

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

The ENST00000400384.7(MAPK4):​c.546+9639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,108 control chromosomes in the GnomAD database, including 40,069 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 0.69 (40069 hom., cov: 32)
• Consequence: MAPK4 ENST00000400384.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.546+9639C>T		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+9639C>T		intron_variant		1	NM_002747.4	ENSP00000383234	P1
MAPK4	ENST00000588540.1	c.546+9639C>T		intron_variant		1		ENSP00000465661
MAPK4	ENST00000592595.5	c.546+9639C>T		intron_variant		1		ENSP00000466233
MAPK4	ENST00000540640.3	c.-87-40936C>T		intron_variant		2		ENSP00000439231

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105366 AN: 151990 Hom.: 40070 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.937

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.693 AC: 105382 AN: 152108 Hom.: 40069 Cov.: 32 AF XY: 0.690 AC XY: 51329 AN XY: 74378

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.752

Alfa AF: 0.759 Hom.: 15064

Bravo AF: 0.675

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.31

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: rs3892158; hg19: chr18-48200513;