18-50719733-C-T

Variant names:

• chr18-50719733-C-T
• rs3794899
• NM_002747.4:c.692-2205C>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.692-2205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,122 control chromosomes in the GnomAD database, including 49,874 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 0.81 (49874 hom., cov: 32)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.692-2205C>T		intron_variant	Intron 3 of 5	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.692-2205C>T		intron_variant	Intron 3 of 5	1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000592595.5	c.691+4510C>T		intron_variant	Intron 3 of 3	1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.59-2205C>T		intron_variant	Intron 2 of 4	2		ENSP00000439231.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122991 AN: 152006 Hom.: 49847 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.809 AC: 123069 AN: 152122 Hom.: 49874 Cov.: 32 AF XY: 0.809 AC XY: 60139 AN XY: 74368

African (AFR) AF: 0.791 AC: 32807 AN: 41474

American (AMR) AF: 0.838 AC: 12815 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4125 AN: 5166

South Asian (SAS) AF: 0.778 AC: 3756 AN: 4826

European-Finnish (FIN) AF: 0.795 AC: 8415 AN: 10582

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55507 AN: 67992

Other (OTH) AF: 0.826 AC: 1742 AN: 2108

Alfa AF: 0.813 Hom.: 10209

Bravo AF: 0.811

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.4
DANN	Benign	0.34
PhyloP100		0.47
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: rs3794899; hg19: chr18-48246103;