Variant 22-50266618-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002751.7(MAPK11):c.611-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,561,010 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 3 hom. )

Consequence

MAPK11
NM_002751.7 splice_region, intron

Scores

Splicing: ADA: 0.009294

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.403

Variant links:

Genes affected

MAPK11 (HGNC:6873): (mitogen-activated protein kinase 11) This gene encodes a member of a family of protein kinases that are involved in the integration of biochemical signals for a wide variety of cellular processes, including cell proliferation, differentiation, transcriptional regulation, and development. The encoded protein can be activated by proinflammatory cytokines and environmental stresses through phosphorylation by mitogen activated protein kinase kinases (MKKs). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

MAPK11 links:

MAPK11 (HGNC:):

MAPK11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 22-50266618-G-A is Benign according to our data. Variant chr22-50266618-G-A is described in ClinVar as [Benign]. Clinvar id is 711784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAPK11	NM_002751.7 linkuse as main transcript	c.611-7C>T	splice_region_variant, intron_variant	ENST00000330651.11	NP_002742.3	Q15759-1
MAPK11	XM_047441447.1 linkuse as main transcript	c.287-7C>T	splice_region_variant, intron_variant		XP_047297403.1
MAPK11	NR_110887.2 linkuse as main transcript	n.699-7C>T	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MAPK11	ENST00000330651.11 linkuse as main transcript	c.611-7C>T	splice_region_variant, intron_variant	1	NM_002751.7	ENSP00000333685.6	Q15759-1
MAPK11	ENST00000395764.5 linkuse as main transcript	n.611-7C>T	splice_region_variant, intron_variant	1		ENSP00000379113.1	Q15759-1
MAPK11	ENST00000417877.1 linkuse as main transcript	n.*123-7C>T	splice_region_variant, intron_variant	5		ENSP00000409136.1	F8WDP4

Frequencies

GnomAD3 genomes

AF:

0.000986

AC:

150

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000432

AC:

AN:

208288

Hom.:

AF XY:

0.000367

AC XY:

AN XY:

111838

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.000535

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000172

AC:

242

AN:

1408786

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

125

AN XY:

695874

show subpopulations

Gnomad4 AFR exome

AF:

0.00358

Gnomad4 AMR exome

AF:

0.000562

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000645

Gnomad4 OTH exome

AF:

0.000379

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152224

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000792

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.8

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0093

dbscSNV1_RF

Benign

0.092

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over