rs17759598

chr22-21767860-T-C

Variant summary

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

The NM_002745.5(MAPK1):c.*9+1335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,108 control chromosomes in the GnomAD database, including 1,014 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 0.10 (1014 hom., cov: 31)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.*9+1335A>G		intron_variant		ENST00000215832.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.*9+1335A>G		intron_variant		1	NM_002745.5	P1
MAPK1	ENST00000491588.1	n.234+1335A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15412 AN: 151990 Hom.: 1015 Cov.: 31

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.101 AC: 15412 AN: 152108 Hom.: 1014 Cov.: 31 AF XY: 0.0981 AC XY: 7291 AN XY: 74336

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.129

Alfa AF: 0.114 Hom.: 200

Bravo AF: 0.101

Asia WGS AF: 0.0440 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.94
Dann	Benign	0.61

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: rs17759598; hg19: chr22-22122149;