dbSNP rs149929003: MAP4:c.*44G>A (chr3-47852890-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001134364.2(MAP4):c.3310G>A(p.Asp1104Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00233 in 1,596,158 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 8 hom. )

Consequence

MAP4
NM_001134364.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.01

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00811401).

BP6

Variant 3-47852890-C-T is Benign according to our data. Variant chr3-47852890-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3043744.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134364.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP4	NM_001385682.1	MANE Select	c.*44G>A		3_prime_UTR	Exon 21 of 21	NP_001372611.1	A0A804HKE7
MAP4	NM_001134364.2		c.3310G>A	p.Asp1104Asn	missense	Exon 18 of 18	NP_001127836.1	P27816-6
MAP4	NM_001384756.1		c.3265G>A	p.Asp1089Asn	missense	Exon 18 of 18	NP_001371685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP4	ENST00000683076.1	MANE Select	c.*44G>A	3_prime_UTR	Exon 21 of 21	ENSP00000507895.1	A0A804HKE7
MAP4	ENST00000360240.10	TSL:1	c.*142G>A	3_prime_UTR	Exon 19 of 19	ENSP00000353375.6	P27816-1
MAP4	ENST00000429422.5	TSL:1	c.*44G>A	3_prime_UTR	Exon 10 of 10	ENSP00000416743.1	H7C4C5

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

236

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00170

AC:

373

AN:

219334

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.000145

Gnomad AMR exome

AF:

0.000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00422

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00162

GnomAD4 exome

AF:

0.00242

AC:

3490

AN:

1443900

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1714

AN XY:

717100

show subpopulations

African (AFR)

AF:

0.000394

AC:

AN:

32962

American (AMR)

AF:

0.000290

AC:

AN:

41338

Ashkenazi Jewish (ASJ)

AF:

0.0000391

AC:

AN:

25602

East Asian (EAS)

AF:

0.0000773

AC:

AN:

38806

South Asian (SAS)

AF:

0.000284

AC:

AN:

84550

European-Finnish (FIN)

AF:

0.00430

AC:

225

AN:

52298

Middle Eastern (MID)

AF:

0.000874

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00273

AC:

3015

AN:

1102962

Other (OTH)

AF:

0.00322

AC:

192

AN:

59664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

210

420

630

840

1050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.00155

AC:

236

AN:

152258

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41552

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00265

AC:

180

AN:

68014

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00220

AC:

ExAC

AF:

0.00154

AC:

186

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MAP4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.34

PhyloP100

6.0

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Uncertain

0.017

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.61

MVP

0.57

ClinPred

0.053

GERP RS

4.7

Mutation Taster

=98/2

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

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