rs8136867

Variant names:

• chr22-21850504-G-A
• rs8136867
• NM_002745.5:c.119+16818C>T

Variant summary

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

The NM_002745.5(MAPK1):​c.119+16818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,952 control chromosomes in the GnomAD database, including 23,400 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 0.55 (23400 hom., cov: 32)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 33 publications found

Genes affected

MAPK1 (HGNC:6871): (mitogen-activated protein kinase 1) This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]

MAPK1 Gene-Disease associations (from GenCC):

• Noonan syndrome 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.119+16818C>T		intron_variant	Intron 1 of 8	ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.119+16818C>T		intron_variant	Intron 1 of 7		NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.119+16818C>T		intron_variant	Intron 1 of 8	1	NM_002745.5	ENSP00000215832.7
MAPK1	ENST00000398822.7	c.119+16818C>T		intron_variant	Intron 1 of 7	1		ENSP00000381803.3
MAPK1	ENST00000544786.1	c.119+16818C>T		intron_variant	Intron 1 of 6	1		ENSP00000440842.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83742 AN: 151834 Hom.: 23365 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.552 AC: 83832 AN: 151952 Hom.: 23400 Cov.: 32 AF XY: 0.545 AC XY: 40506 AN XY: 74262

African (AFR) AF: 0.607 AC: 25144 AN: 41436

American (AMR) AF: 0.623 AC: 9508 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2168 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2311 AN: 5168

South Asian (SAS) AF: 0.471 AC: 2273 AN: 4826

European-Finnish (FIN) AF: 0.378 AC: 3969 AN: 10508

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36531 AN: 67964

Other (OTH) AF: 0.591 AC: 1250 AN: 2116

Alfa AF: 0.545 Hom.: 86433

Bravo AF: 0.570

Asia WGS AF: 0.475 AC: 1650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		0.011
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: rs8136867; hg19: chr22-22204793;