3-47998793-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.68G>A(p.Arg23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,613,960 control chromosomes in the GnomAD database, including 4,031 homozygotes. In-silico tool predicts 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. R23W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.047 ( 222 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3809 hom. )

Consequence

MAP4
NM_001385682.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.53

Publications

43 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=0.0023638904).

BP6

Variant 3-47998793-C-T is Benign according to our data. Variant chr3-47998793-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056736.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1 link	c.68G>A	p.Arg23Gln	missense_variant	Exon 2 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.68G>A	p.Arg23Gln	missense_variant	Exon 2 of 21		NM_001385682.1	ENSP00000507895.1		A0A804HKE7

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7124

AN:

152164

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0416

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0478

GnomAD2 exomes

AF:

0.0526

AC:

13217

AN:

251290

AF XY:

0.0553

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0233

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0415

Gnomad NFE exome

AF:

0.0781

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0682

AC:

99679

AN:

1461678

Hom.:

3809

Cov.:

AF XY:

0.0683

AC XY:

49638

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.0100

AC:

336

AN:

33480

American (AMR)

AF:

0.0260

AC:

1163

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

1417

AN:

26134

East Asian (EAS)

AF:

0.000227

AC:

AN:

39696

South Asian (SAS)

AF:

0.0492

AC:

4248

AN:

86254

European-Finnish (FIN)

AF:

0.0459

AC:

2450

AN:

53420

Middle Eastern (MID)

AF:

0.0867

AC:

500

AN:

5768

European-Non Finnish (NFE)

AF:

0.0773

AC:

85938

AN:

1111818

Other (OTH)

AF:

0.0599

AC:

3618

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4816

9632

14448

19264

24080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3118

6236

9354

12472

15590

<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:

0.0468

AC:

7122

AN:

152282

Hom.:

222

Cov.:

AF XY:

0.0442

AC XY:

3293

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0141

AC:

585

AN:

41552

American (AMR)

AF:

0.0337

AC:

516

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0504

AC:

175

AN:

3470

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.0504

AC:

243

AN:

4822

European-Finnish (FIN)

AF:

0.0416

AC:

441

AN:

10606

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0734

AC:

4990

AN:

68024

Other (OTH)

AF:

0.0468

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

346

692

1037

1383

1729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0665

Hom.:

1488

Bravo

AF:

0.0443

TwinsUK

AF:

0.0831

AC:

308

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.0781

AC:

672

ExAC

AF:

0.0546

AC:

6635

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0764

EpiControl

AF:

0.0776

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP4-related disorder

Benign:1

Dec 04, 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

0.34

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

.;T;T;T;.;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.93

D;D;D;D;D;.;D;D

MetaRNN

Benign

0.0024

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.;.;M;M;.

PhyloP100

2.5

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.1

N;N;N;.;.;D;D;.

REVEL

Benign

0.11

Sift

Benign

0.037

D;D;D;.;.;T;T;.

Sift4G

Benign

0.39

T;D;T;.;.;D;D;D

Polyphen

1.0

D;.;D;.;.;.;.;.

Vest4

0.29

MPC

0.53

ClinPred

0.027

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.033

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over