Genetic Variant MAP3K11:c.2207-93C>G (chr11-65598721-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002419.4(MAP3K11):c.2207-93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 931,276 control chromosomes in the GnomAD database, including 27,833 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 0.20 ( 3425 hom., cov: 33)

Exomes 𝑓: 0.25 ( 24408 hom. )

Consequence

MAP3K11
NM_002419.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182

Publications

19 publications found

Variant links:

Genes affected

MAP3K11 (HGNC:6850): (mitogen-activated protein kinase kinase kinase 11) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]

MAP3K11 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002419.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K11	NM_002419.4	MANE Select	c.2207-93C>G		intron	N/A	NP_002410.1	Q16584-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP3K11	ENST00000309100.8	TSL:1 MANE Select	c.2207-93C>G	intron	N/A	ENSP00000309597.3	Q16584-1
MAP3K11	ENST00000850884.1		c.2207-93C>G	intron	N/A	ENSP00000520962.1
MAP3K11	ENST00000941368.1		c.2204-96C>G	intron	N/A	ENSP00000611427.1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30611

AN:

152014

Hom.:

3426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.245

AC:

190934

AN:

779142

Hom.:

24408

AF XY:

0.244

AC XY:

94174

AN XY:

386440

show subpopulations

African (AFR)

AF:

0.138

AC:

2404

AN:

17376

American (AMR)

AF:

0.174

AC:

2260

AN:

12954

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

4093

AN:

14498

East Asian (EAS)

AF:

0.165

AC:

4578

AN:

27738

South Asian (SAS)

AF:

0.159

AC:

6458

AN:

40710

European-Finnish (FIN)

AF:

0.181

AC:

6357

AN:

35112

Middle Eastern (MID)

AF:

0.326

AC:

1329

AN:

4076

European-Non Finnish (NFE)

AF:

0.262

AC:

154931

AN:

590992

Other (OTH)

AF:

0.239

AC:

8524

AN:

35686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

7548

15096

22645

30193

37741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4610

9220

13830

18440

23050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.201

AC:

30602

AN:

152134

Hom.:

3425

Cov.:

AF XY:

0.193

AC XY:

14366

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.138

AC:

5723

AN:

41510

American (AMR)

AF:

0.168

AC:

2574

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

982

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

795

AN:

5170

South Asian (SAS)

AF:

0.139

AC:

671

AN:

4822

European-Finnish (FIN)

AF:

0.162

AC:

1720

AN:

10600

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17309

AN:

67952

Other (OTH)

AF:

0.206

AC:

435

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1271

2542

3813

5084

6355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.111

Hom.:

177

Bravo

AF:

0.203

Asia WGS

AF:

0.115

AC:

401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.3

(source)

DANN

Benign

0.78

PhyloP100

-0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over