rs2283792

chr22-21776836-T-G

Variant summary

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

The NM_002745.5(MAPK1):c.857-3854A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,890 control chromosomes in the GnomAD database, including 22,411 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 0.54 (22411 hom., cov: 31)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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 (AMR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK1	NM_002745.5	c.857-3854A>C		intron_variant		ENST00000215832.11
MAPK1	NM_138957.3	c.857-3854A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK1	ENST00000215832.11	c.857-3854A>C		intron_variant		1	NM_002745.5	P1
MAPK1	ENST00000398822.7	c.857-3854A>C		intron_variant		1		P1
MAPK1	ENST00000544786.1	c.725-3854A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81791 AN: 151772 Hom.: 22373 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.539 AC: 81887 AN: 151890 Hom.: 22411 Cov.: 31 AF XY: 0.534 AC XY: 39595 AN XY: 74212

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.580

Alfa AF: 0.525 Hom.: 28323

Bravo AF: 0.559

Asia WGS AF: 0.473 AC: 1645 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	2.1
Dann	Benign	0.73

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: rs2283792; hg19: chr22-22131125; COSMIC: COSV53189737;