rs2876981

chr22-21851322-A-Cchr22-21851322-A-G

Variant summary

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

The NM_002745.5(MAPK1):c.119+16000T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,074 control chromosomes in the GnomAD database, including 7,579 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 0.30 (7579 hom., cov: 30)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.119+16000T>G		intron_variant		ENST00000215832.11
MAPK1	NM_138957.3	c.119+16000T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.119+16000T>G		intron_variant		1	NM_002745.5	P1
MAPK1	ENST00000398822.7	c.119+16000T>G		intron_variant		1		P1
MAPK1	ENST00000544786.1	c.119+16000T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45922 AN: 151956 Hom.: 7579 Cov.: 30

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.302 AC: 45926 AN: 152074 Hom.: 7579 Cov.: 30 AF XY: 0.294 AC XY: 21870 AN XY: 74344

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.347

Alfa AF: 0.330 Hom.: 2899

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.1
Dann	Benign	0.57

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: rs2876981; hg19: chr22-22205611;