chr15-43525854-G-A

Variant names:

• chr15-43525854-G-A
• rs2245715
• NM_002373.6:c.4381G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002373.6(MAP1A):​c.4381G>A​(p.Asp1461Asn) variant causes a missense change. The variant allele was found at a frequency of 0.147 in 1,610,258 control chromosomes in the GnomAD database, including 30,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (9125 hom., cov: 32)
  • Exomes 𝑓: 0.13 (20941 hom.)
• Consequence: MAP1A NM_002373.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7787941E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002373.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1A	NM_002373.6	MANE Select	c.4381G>A	p.Asp1461Asn	missense	Exon 4 of 6	NP_002364.5
	MAP1A	NM_001411089.1		c.5095G>A	p.Asp1699Asn	missense	Exon 5 of 7	NP_001398018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1A	ENST00000300231.6	TSL:5 MANE Select	c.4381G>A	p.Asp1461Asn	missense	Exon 4 of 6	ENSP00000300231.5
	MAP1A	ENST00000382031.5	TSL:5	c.5095G>A	p.Asp1699Asn	missense	Exon 5 of 7	ENSP00000371462.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40459 AN: 151832 Hom.: 9103 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.190 AC: 47158 AN: 248060 AF XY: 0.181

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.0755

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.134 AC: 195669 AN: 1458308 Hom.: 20941 Cov.: 56 AF XY: 0.135 AC XY: 97754 AN XY: 725366

African (AFR) AF: 0.636 AC: 21168 AN: 33296

American (AMR) AF: 0.209 AC: 9300 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 5046 AN: 26082

East Asian (EAS) AF: 0.433 AC: 17200 AN: 39698

South Asian (SAS) AF: 0.208 AC: 17839 AN: 85868

European-Finnish (FIN) AF: 0.0761 AC: 4049 AN: 53212

Middle Eastern (MID) AF: 0.153 AC: 884 AN: 5764

European-Non Finnish (NFE) AF: 0.0991 AC: 110003 AN: 1109652

Other (OTH) AF: 0.169 AC: 10180 AN: 60234

GnomAD4 genome AF: 0.267 AC: 40535 AN: 151950 Hom.: 9125 Cov.: 32 AF XY: 0.264 AC XY: 19594 AN XY: 74322

African (AFR) AF: 0.609 AC: 25170 AN: 41298

American (AMR) AF: 0.211 AC: 3219 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2233 AN: 5176

South Asian (SAS) AF: 0.227 AC: 1091 AN: 4814

European-Finnish (FIN) AF: 0.0798 AC: 845 AN: 10588

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0982 AC: 6676 AN: 68006

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.156 Hom.: 7365

Bravo AF: 0.298

TwinsUK AF: 0.0952 AC: 353

ALSPAC AF: 0.108 AC: 417

ESP6500AA AF: 0.589 AC: 2194

ESP6500EA AF: 0.102 AC: 839

ExAC AF: 0.195 AC: 23595

Asia WGS AF: 0.349 AC: 1213 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.000018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.097
Sift	Benign	0.088	T
Sift4G	Benign	0.35	T
Polyphen		0.14	B
Vest4		0.042
MPC		0.53
ClinPred		0.036	T
GERP RS		3.0
Varity_R		0.078
gMVP		0.018
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2245715; hg19: chr15-43818052; COSMIC: COSV55806221;