dbSNP rs1063311: MAPK1:c.*2072G>A (chr22-21762178-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002745.5(MAPK1):c.*2072G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,050 control chromosomes in the GnomAD database, including 10,985 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 0.38 ( 10985 hom., cov: 32)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

MAPK1
NM_002745.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.596

Publications

26 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5 link	c.*2072G>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.*2072G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_002745.5	ENSP00000215832.7		P28482-1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57053

AN:

151916

Hom.:

10987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.375

AC:

57074

AN:

152034

Hom.:

10985

Cov.:

AF XY:

0.368

AC XY:

27355

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.332

AC:

13755

AN:

41482

American (AMR)

AF:

0.386

AC:

5896

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1692

AN:

3468

East Asian (EAS)

AF:

0.208

AC:

1077

AN:

5180

South Asian (SAS)

AF:

0.326

AC:

1571

AN:

4822

European-Finnish (FIN)

AF:

0.287

AC:

3032

AN:

10564

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28621

AN:

67938

Other (OTH)

AF:

0.426

AC:

898

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1805

3611

5416

7222

9027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.400

Hom.:

6340

Bravo

AF:

0.381

Asia WGS

AF:

0.258

AC:

901

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.74

(source)

DANN

Benign

0.44

PhyloP100

-0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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