NM_005909.5:c.286+92T>C

Variant names:

• chr5-72115891-T-C
• rs1531312
• NM_005909.5:c.286+92T>C

Variant summary

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

The NM_005909.5(MAP1B):​c.286+92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 839,288 control chromosomes in the GnomAD database, including 194,516 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 0.64 (32223 hom., cov: 32)
  • Exomes 𝑓: 0.68 (162293 hom.)
• Consequence: MAP1B NM_005909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 8 publications found

Genes affected

MAP1B (HGNC:6836): (microtubule associated protein 1B) 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 MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system. [provided by RefSeq, Jul 2008]

MAP1B Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• periventricular nodular heterotopia 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005909.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1B	NM_005909.5	MANE Select	c.286+92T>C		intron	N/A	NP_005900.2	P46821

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1B	ENST00000296755.12	TSL:1 MANE Select	c.286+92T>C		intron	N/A	ENSP00000296755.7	P46821
	MAP1B	ENST00000511641.2	TSL:1	c.286+92T>C		intron	N/A	ENSP00000423444.2	D6RA32
	MAP1B	ENST00000512974.5	TSL:4	c.286+92T>C		intron	N/A	ENSP00000426312.1	D6RGJ3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97806 AN: 151904 Hom.: 32205 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.680 AC: 467489 AN: 687266 Hom.: 162293 Cov.: 9 AF XY: 0.683 AC XY: 251082 AN XY: 367564

African (AFR) AF: 0.541 AC: 9884 AN: 18286

American (AMR) AF: 0.597 AC: 23228 AN: 38888

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 15534 AN: 20198

East Asian (EAS) AF: 0.341 AC: 12073 AN: 35432

South Asian (SAS) AF: 0.659 AC: 44456 AN: 67412

European-Finnish (FIN) AF: 0.737 AC: 35691 AN: 48454

Middle Eastern (MID) AF: 0.742 AC: 3037 AN: 4094

European-Non Finnish (NFE) AF: 0.714 AC: 299963 AN: 419888

Other (OTH) AF: 0.682 AC: 23623 AN: 34614

GnomAD4 genome AF: 0.644 AC: 97878 AN: 152022 Hom.: 32223 Cov.: 32 AF XY: 0.641 AC XY: 47630 AN XY: 74292

African (AFR) AF: 0.540 AC: 22375 AN: 41428

American (AMR) AF: 0.607 AC: 9278 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1759 AN: 5172

South Asian (SAS) AF: 0.643 AC: 3096 AN: 4818

European-Finnish (FIN) AF: 0.729 AC: 7698 AN: 10562

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48644 AN: 67976

Other (OTH) AF: 0.674 AC: 1423 AN: 2112

Alfa AF: 0.693 Hom.: 151601

Bravo AF: 0.631

Asia WGS AF: 0.531 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.4
DANN	Benign	0.87
PhyloP100		-0.057
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: rs1531312; hg19: chr5-71411718; COSMIC: COSV57095796;