Genetic Variant MAP1A:p.Pro776Pro (chr15-43523801-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002373.6(MAP1A):c.2328C>T(p.Pro776Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,830 control chromosomes in the GnomAD database, including 28,835 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 0.17 ( 2359 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26476 hom. )

Consequence

MAP1A
NM_002373.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

20 publications found

Variant links:

Genes affected

MAP1A (HGNC:6835): (microtubule associated protein 1A) This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1A heavy chain and LC2 light chain. Expression of this gene is almost exclusively in the brain. Studies of the rat microtubule-associated protein 1A gene suggested a role in early events of spinal cord development. [provided by RefSeq, Jul 2008]

MAP1A links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1A	NM_002373.6 link	c.2328C>T	p.Pro776Pro	synonymous_variant	Exon 4 of 6	ENST00000300231.6	NP_002364.5
MAP1A	NM_001411089.1 link	c.3042C>T	p.Pro1014Pro	synonymous_variant	Exon 5 of 7		NP_001398018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP1A	ENST00000300231.6 link	c.2328C>T	p.Pro776Pro	synonymous_variant	Exon 4 of 6	5	NM_002373.6	ENSP00000300231.5
MAP1A	ENST00000382031.5 link	c.3042C>T	p.Pro1014Pro	synonymous_variant	Exon 5 of 7	5		ENSP00000371462.1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25867

AN:

152030

Hom.:

2362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.161

AC:

40045

AN:

248040

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.00251

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.184

AC:

269073

AN:

1461680

Hom.:

26476

Cov.:

AF XY:

0.186

AC XY:

134978

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.172

AC:

5775

AN:

33480

American (AMR)

AF:

0.108

AC:

4834

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5584

AN:

26136

East Asian (EAS)

AF:

0.00146

AC:

AN:

39700

South Asian (SAS)

AF:

0.214

AC:

18438

AN:

86252

European-Finnish (FIN)

AF:

0.131

AC:

7007

AN:

53306

Middle Eastern (MID)

AF:

0.261

AC:

1507

AN:

5768

European-Non Finnish (NFE)

AF:

0.193

AC:

214933

AN:

1111936

Other (OTH)

AF:

0.181

AC:

10937

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14300

28599

42899

57198

71498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7396

14792

22188

29584

36980

<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:

0.170

AC:

25875

AN:

152150

Hom.:

2359

Cov.:

AF XY:

0.166

AC XY:

12377

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.172

AC:

7151

AN:

41492

American (AMR)

AF:

0.146

AC:

2224

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

747

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5184

South Asian (SAS)

AF:

0.186

AC:

898

AN:

4828

European-Finnish (FIN)

AF:

0.125

AC:

1331

AN:

10610

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12943

AN:

67964

Other (OTH)

AF:

0.183

AC:

386

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1111

2221

3332

4442

5553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.191

Hom.:

1561

Bravo

AF:

0.170

Asia WGS

AF:

0.0840

AC:

296

AN:

3476

EpiCase

AF:

0.196

EpiControl

AF:

0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.2

(source)

DANN

Benign

0.60

PhyloP100

-0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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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