rs8136867

Positions:

• chr22-21850504-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.119+16818C>T		intron_variant		ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.119+16818C>T		intron_variant			NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.119+16818C>T		intron_variant		1	NM_002745.5	ENSP00000215832	P1
MAPK1	ENST00000398822.7	c.119+16818C>T		intron_variant		1		ENSP00000381803	P1
MAPK1	ENST00000544786.1	c.119+16818C>T		intron_variant		1		ENSP00000440842

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

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.591

Alfa AF: 0.551 Hom.: 36448

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

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: rs8136867; hg19: chr22-22204793;