rs8141815

Variant names:

• chr22-21837296-G-A
• rs8141815
• NM_002745.5:c.120-29450C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-21837296-G-A
• chr22-21837296-G-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.120-29450C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,194 control chromosomes in the GnomAD database, including 260 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 0.053 (260 hom., cov: 32)
• Consequence: MAPK1 NM_002745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5	c.120-29450C>T		intron_variant	Intron 1 of 8	ENST00000215832.11	NP_002736.3
MAPK1	NM_138957.3	c.120-29450C>T		intron_variant	Intron 1 of 7		NP_620407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11	c.120-29450C>T		intron_variant	Intron 1 of 8	1	NM_002745.5	ENSP00000215832.7
MAPK1	ENST00000398822.7	c.120-29450C>T		intron_variant	Intron 1 of 7	1		ENSP00000381803.3
MAPK1	ENST00000544786.1	c.120-29450C>T		intron_variant	Intron 1 of 6	1		ENSP00000440842.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8126 AN: 152074 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0534 AC: 8122 AN: 152194 Hom.: 260 Cov.: 32 AF XY: 0.0534 AC XY: 3973 AN XY: 74412

African (AFR) AF: 0.0550 AC: 2284 AN: 41526

American (AMR) AF: 0.0679 AC: 1038 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.108 AC: 558 AN: 5174

South Asian (SAS) AF: 0.113 AC: 547 AN: 4820

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10604

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0432 AC: 2939 AN: 67996

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0490 Hom.: 346

Bravo AF: 0.0561

Asia WGS AF: 0.0960 AC: 335 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	1.7
DANN	Benign	0.45
PhyloP100		-0.42
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: rs8141815; hg19: chr22-22191585;