dbSNP rs7286558: MAPK1:c.120-18048G>A (chr22-21825894-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.120-18048G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,242 control chromosomes in the GnomAD database, including 188 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 0.044 ( 188 hom., cov: 32)

Consequence

MAPK1
NM_002745.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

Publications

8 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:

ENSG00000289564 (HGNC:):

ENSG00000289564 links:

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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=-0.37).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK1	NM_002745.5 link	c.120-18048G>A		intron_variant	Intron 1 of 8	ENST00000215832.11	NP_002736.3	P28482-1Q1HBJ4Q499G7
MAPK1	NM_138957.3 link	c.120-18048G>A		intron_variant	Intron 1 of 7		NP_620407.1	P28482-1Q1HBJ4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAPK1	ENST00000215832.11 link	c.120-18048G>A	intron_variant	Intron 1 of 8	1	NM_002745.5	ENSP00000215832.7	P28482-1
MAPK1	ENST00000398822.7 link	c.120-18048G>A	intron_variant	Intron 1 of 7	1		ENSP00000381803.3	P28482-1
MAPK1	ENST00000544786.1 link	c.120-18048G>A	intron_variant	Intron 1 of 6	1		ENSP00000440842.1	P28482-2
ENSG00000289564	ENST00000687533.2 link	n.286+8726C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0442

AC:

6729

AN:

152126

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0554

Gnomad OTH

AF:

0.0544

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

GnomAD4 genome

AF:

0.0443

AC:

6737

AN:

152242

Hom.:

188

Cov.:

AF XY:

0.0428

AC XY:

3185

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0233

AC:

967

AN:

41538

American (AMR)

AF:

0.0600

AC:

919

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

368

AN:

3472

East Asian (EAS)

AF:

0.0230

AC:

119

AN:

5182

South Asian (SAS)

AF:

0.0299

AC:

144

AN:

4824

European-Finnish (FIN)

AF:

0.0281

AC:

298

AN:

10602

Middle Eastern (MID)

AF:

0.121

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0555

AC:

3771

AN:

68002

Other (OTH)

AF:

0.0539

AC:

114

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

341

682

1024

1365

1706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0500

Hom.:

100

Bravo

AF:

0.0454

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.66

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