rs1869258

Positions:

• chr15-43511423-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001411089.1(MAP1A):​c.238+197A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,934 control chromosomes in the GnomAD database, including 21,113 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 0.46 (21113 hom., cov: 32)
• Consequence: MAP1A NM_001411089.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1A	NM_001411089.1	c.238+197A>C		intron_variant			NP_001398018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP1A	ENST00000382031.5	c.238+197A>C		intron_variant		5		ENSP00000371462.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70233 AN: 151814 Hom.: 21056 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.429

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70342 AN: 151934 Hom.: 21113 Cov.: 32 AF XY: 0.456 AC XY: 33814 AN XY: 74234

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.431

Alfa AF: 0.346 Hom.: 4989

Bravo AF: 0.492

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1869258; hg19: chr15-43803621;