18-50568984-G-A

Variant names:

• chr18-50568984-G-A
• rs728682
• NM_002747.4:c.-871+8741G>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.-871+8741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,022 control chromosomes in the GnomAD database, including 13,525 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 0.41 (13525 hom., cov: 32)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.-871+8741G>A		intron_variant	Intron 1 of 5	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.-871+8741G>A		intron_variant	Intron 1 of 5	1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000588540.1	c.-871+8225G>A		intron_variant	Intron 1 of 2	1		ENSP00000465661.1
MAPK4	ENST00000592595.5	c.-871+8741G>A		intron_variant	Intron 1 of 3	1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.-88+8741G>A		intron_variant	Intron 1 of 4	2		ENSP00000439231.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61849 AN: 151904 Hom.: 13529 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.407 AC: 61855 AN: 152022 Hom.: 13525 Cov.: 32 AF XY: 0.408 AC XY: 30341 AN XY: 74294

African (AFR) AF: 0.223 AC: 9245 AN: 41476

American (AMR) AF: 0.463 AC: 7074 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1561 AN: 3462

East Asian (EAS) AF: 0.384 AC: 1984 AN: 5168

South Asian (SAS) AF: 0.428 AC: 2061 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5471 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33020 AN: 67942

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.433 Hom.: 1960

Bravo AF: 0.399

Asia WGS AF: 0.350 AC: 1213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		-0.19
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: rs728682; hg19: chr18-48095354;