rs2283792

Variant names:

• chr22-21776836-T-G
• rs2283792
• NM_002745.5:c.857-3854A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 88 publications found

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]

MAPK1 Gene-Disease associations (from GenCC):

• Noonan syndrome 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.857-3854A>C		intron_variant	Intron 6 of 8	ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.857-3854A>C		intron_variant	Intron 6 of 7		NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.857-3854A>C		intron_variant	Intron 6 of 8	1	NM_002745.5	ENSP00000215832.7
MAPK1	ENST00000398822.7	c.857-3854A>C		intron_variant	Intron 6 of 7	1		ENSP00000381803.3
MAPK1	ENST00000544786.1	c.725-3854A>C		intron_variant	Intron 5 of 6	1		ENSP00000440842.1

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

African (AFR) AF: 0.604 AC: 25024 AN: 41424

American (AMR) AF: 0.612 AC: 9336 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2307 AN: 5174

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4808

European-Finnish (FIN) AF: 0.359 AC: 3785 AN: 10540

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35214 AN: 67918

Other (OTH) AF: 0.580 AC: 1221 AN: 2104

Alfa AF: 0.523 Hom.: 73304

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
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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