rs2298432

Positions:

• chr22-21768900-A-C
• chr22-21768900-A-T

Variant summary

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

The NM_002745.5(MAPK1):​c.*9+295T>G 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 205,208 control chromosomes in the GnomAD database, including 51,389 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 0.72 (40493 hom., cov: 32)
  • Exomes 𝑓: 0.63 (10896 hom.)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.*9+295T>G		intron_variant		ENST00000215832.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.*9+295T>G		intron_variant		1	NM_002745.5	P1
MAPK1	ENST00000491588.1	n.234+295T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108700 AN: 152020 Hom.: 40430 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.631 AC: 33472 AN: 53070 Hom.: 10896 AF XY: 0.630 AC XY: 17243 AN XY: 27386

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.715 AC: 108824 AN: 152138 Hom.: 40493 Cov.: 32 AF XY: 0.712 AC XY: 52983 AN XY: 74368

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.725

Alfa AF: 0.642 Hom.: 43899

Bravo AF: 0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.041
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2298432; hg19: chr22-22123189;