Genetic Variant NM_001135553.4:c.458-758A>G (chr1-46569256-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_001135553.4(MKNK1):c.458-758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,282 control chromosomes in the GnomAD database, including 8,491 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 0.32 ( 8489 hom., cov: 33)

Exomes 𝑓: 0.21 ( 2 hom. )

Consequence

MKNK1
NM_001135553.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.460

Publications

8 publications found

Variant links:

Genes affected

MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

MKNK1 links:

MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

MKNK1-AS1 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135553.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MKNK1	NM_001135553.4	MANE Select	c.458-758A>G	intron	N/A	NP_001129025.2
MKNK1-AS1	NR_038403.1		n.1446T>C	non_coding_transcript_exon	Exon 8 of 8
MKNK1	NM_003684.7		c.581-758A>G	intron	N/A	NP_003675.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MKNK1	ENST00000371945.10	TSL:1 MANE Select	c.458-758A>G	intron	N/A	ENSP00000361013.5
MKNK1	ENST00000371946.9	TSL:1	c.581-758A>G	intron	N/A	ENSP00000361014.5
MKNK1	ENST00000342571.7	TSL:1	n.484-758A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49115

AN:

152060

Hom.:

8481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.327

GnomAD4 exome

AF:

0.212

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.178

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.211

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.323

AC:

49155

AN:

152178

Hom.:

8489

Cov.:

AF XY:

0.324

AC XY:

24085

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.453

AC:

18810

AN:

41502

American (AMR)

AF:

0.366

AC:

5593

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

980

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1393

AN:

5176

South Asian (SAS)

AF:

0.249

AC:

1204

AN:

4826

European-Finnish (FIN)

AF:

0.240

AC:

2542

AN:

10598

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17674

AN:

67998

Other (OTH)

AF:

0.324

AC:

684

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1648

3295

4943

6590

8238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.301

Hom.:

1945

Bravo

AF:

0.336

Asia WGS

AF:

0.251

AC:

876

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

5.7

(source)

DANN

Benign

0.59

PhyloP100

0.46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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