dbSNP rs1784223: MAP3K11:c.739+241A>G (chr11-65612777-T-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.739+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 403,374 control chromosomes in the GnomAD database, including 21,669 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 0.33 ( 8901 hom., cov: 33)

Exomes 𝑓: 0.31 ( 12768 hom. )

Consequence

MAP3K11
NM_002419.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

8 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K11	NM_002419.4	MANE Select	c.739+241A>G		intron	N/A	NP_002410.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAP3K11	ENST00000309100.8	TSL:1 MANE Select	c.739+241A>G	intron	N/A	ENSP00000309597.3
MAP3K11	ENST00000527304.1	TSL:6	n.1460A>G	non_coding_transcript_exon	Exon 1 of 1
MAP3K11	ENST00000850884.1		c.739+241A>G	intron	N/A	ENSP00000520962.1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50597

AN:

151998

Hom.:

8904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.308

AC:

77300

AN:

251256

Hom.:

12768

Cov.:

AF XY:

0.305

AC XY:

38989

AN XY:

127686

show subpopulations

African (AFR)

AF:

0.413

AC:

2969

AN:

7184

American (AMR)

AF:

0.260

AC:

2247

AN:

8632

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

2755

AN:

9014

East Asian (EAS)

AF:

0.113

AC:

2496

AN:

22136

South Asian (SAS)

AF:

0.126

AC:

615

AN:

4880

European-Finnish (FIN)

AF:

0.251

AC:

4927

AN:

19648

Middle Eastern (MID)

AF:

0.346

AC:

450

AN:

1300

European-Non Finnish (NFE)

AF:

0.342

AC:

55533

AN:

162160

Other (OTH)

AF:

0.326

AC:

5308

AN:

16302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2443

4885

7328

9770

12213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.333

AC:

50609

AN:

152118

Hom.:

8901

Cov.:

AF XY:

0.318

AC XY:

23674

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.408

AC:

16909

AN:

41478

American (AMR)

AF:

0.285

AC:

4357

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1074

AN:

3468

East Asian (EAS)

AF:

0.123

AC:

639

AN:

5184

South Asian (SAS)

AF:

0.134

AC:

645

AN:

4828

European-Finnish (FIN)

AF:

0.224

AC:

2374

AN:

10602

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23379

AN:

67950

Other (OTH)

AF:

0.350

AC:

740

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.340

Hom.:

11361

Bravo

AF:

0.343

Asia WGS

AF:

0.142

AC:

499

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.7

(source)

DANN

Benign

0.83

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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