Genetic Variant NM_005456.4:c.-5C>G (chr11-45885816-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005456.4(MAPK8IP1):c.-5C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,421,284 control chromosomes in the GnomAD database, including 26 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 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 24 hom. )

Consequence

MAPK8IP1
NM_005456.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

0 publications found

Variant links:

Genes affected

MAPK8IP1 (HGNC:6882): (mitogen-activated protein kinase 8 interacting protein 1) This gene encodes a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and to decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes. [provided by RefSeq, May 2011]

MAPK8IP1 Gene-Disease associations (from GenCC):

diabetes mellitus, noninsulin-dependent
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MAPK8IP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BS2

High AC in GnomAd4 at 410 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8IP1	NM_005456.4 link	c.-5C>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000241014.6	NP_005447.1	Q9UQF2Q6NUQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8IP1	ENST00000241014.6 link	c.-5C>G		5_prime_UTR_variant	Exon 1 of 12	1	NM_005456.4	ENSP00000241014.2		Q9UQF2

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

410

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00472

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00277

AC:

148

AN:

53522

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000909

Gnomad ASJ exome

AF:

0.000240

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00428

AC:

5426

AN:

1269128

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

2700

AN XY:

621536

show subpopulations

African (AFR)

AF:

0.000465

AC:

AN:

25820

American (AMR)

AF:

0.00122

AC:

AN:

21348

Ashkenazi Jewish (ASJ)

AF:

0.000190

AC:

AN:

21052

East Asian (EAS)

AF:

0.000832

AC:

AN:

27634

South Asian (SAS)

AF:

0.00483

AC:

310

AN:

64178

European-Finnish (FIN)

AF:

0.00171

AC:

AN:

34590

Middle Eastern (MID)

AF:

0.00120

AC:

AN:

4162

European-Non Finnish (NFE)

AF:

0.00468

AC:

4767

AN:

1017948

Other (OTH)

AF:

0.00420

AC:

220

AN:

52396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

253

507

760

1014

1267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.00269

AC:

410

AN:

152156

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41542

American (AMR)

AF:

0.00177

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00472

AC:

321

AN:

67938

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000656

Hom.:

Bravo

AF:

0.00262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.0070

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over