Genetic Variant MAPK1:c.*310G>A (chr22-21763940-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002745.5(MAPK1):c.*310G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0206 in 152,694 control chromosomes in the GnomAD database, including 59 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 0.020 ( 59 hom., cov: 32)

Exomes 𝑓: 0.060 ( 0 hom. )

Consequence

MAPK1
NM_002745.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.67

Publications

7 publications found

Variant links:

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

MAPK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BA1

GnomAdExome4 highest population allele frequency = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5 link	c.*310G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000215832.11	NP_002736.3	P28482-1Q1HBJ4Q499G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK1	ENST00000215832.11 link	c.*310G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_002745.5	ENSP00000215832.7		P28482-1
MAPK1	ENST00000491588.1 link	n.*44G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3112

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.00590

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0656

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.0600

AC:

AN:

450

Hom.:

Cov.:

AF XY:

0.0662

AC XY:

AN XY:

272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0646

AC:

AN:

418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0204

AC:

3111

AN:

152244

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1626

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00609

AC:

253

AN:

41556

American (AMR)

AF:

0.00589

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0656

AC:

695

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0290

AC:

1974

AN:

68018

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

312

467

623

779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0269

Hom.:

Bravo

AF:

0.0159

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

3.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over