3-47914934-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001385682.1(MAP4):c.1882G>A(p.Val628Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,292 control chromosomes in the GnomAD database, including 85,574 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V628A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.37 ( 11044 hom., cov: 31)

Exomes 𝑓: 0.31 ( 74530 hom. )

Consequence

MAP4
NM_001385682.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0770

Publications

50 publications found

Variant links:

Genes affected

MAP4 (HGNC:6862): (microtubule associated protein 4) The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

MAP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1159465E-4).

BP6

Variant 3-47914934-C-T is Benign according to our data. Variant chr3-47914934-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060070.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1 link	c.1882G>A	p.Val628Ile	missense_variant	Exon 8 of 21	ENST00000683076.1	NP_001372611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4	ENST00000683076.1 link	c.1882G>A	p.Val628Ile	missense_variant	Exon 8 of 21		NM_001385682.1	ENSP00000507895.1		A0A804HKE7

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55493

AN:

151664

Hom.:

11031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.331

AC:

83172

AN:

251392

AF XY:

0.329

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.315

AC:

460073

AN:

1461510

Hom.:

74530

Cov.:

AF XY:

0.317

AC XY:

230245

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.526

AC:

17609

AN:

33478

American (AMR)

AF:

0.375

AC:

16757

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9743

AN:

26126

East Asian (EAS)

AF:

0.270

AC:

10699

AN:

39688

South Asian (SAS)

AF:

0.373

AC:

32144

AN:

86242

European-Finnish (FIN)

AF:

0.219

AC:

11689

AN:

53408

Middle Eastern (MID)

AF:

0.383

AC:

2211

AN:

5766

European-Non Finnish (NFE)

AF:

0.305

AC:

339061

AN:

1111710

Other (OTH)

AF:

0.334

AC:

20160

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

15469

30938

46406

61875

77344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11356

22712

34068

45424

56780

<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:

0.366

AC:

55555

AN:

151782

Hom.:

11044

Cov.:

AF XY:

0.361

AC XY:

26803

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.524

AC:

21677

AN:

41364

American (AMR)

AF:

0.379

AC:

5778

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1312

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1412

AN:

5138

South Asian (SAS)

AF:

0.367

AC:

1760

AN:

4800

European-Finnish (FIN)

AF:

0.210

AC:

2214

AN:

10532

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20220

AN:

67918

Other (OTH)

AF:

0.386

AC:

811

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1668

3336

5004

6672

8340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.336

Hom.:

24064

Bravo

AF:

0.386

TwinsUK

AF:

0.314

AC:

1166

ALSPAC

AF:

0.299

AC:

1154

ESP6500AA

AF:

0.534

AC:

2353

ESP6500EA

AF:

0.313

AC:

2696

ExAC

AF:

0.334

AC:

40513

Asia WGS

AF:

0.352

AC:

1223

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.318

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP4-related disorder

Benign:1

Oct 25, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.019

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.00011

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;.;L

PhyloP100

-0.077

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.054

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.22

B;.;P

Vest4

0.053

MPC

0.076

ClinPred

0.0027

GERP RS

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.019

gMVP

0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over