chr5-72114529-G-C

Variant names:

• chr5-72114529-G-C
• rs2199161
• NM_005909.5:c.185-1169G>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.185-1169G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,226 control chromosomes in the GnomAD database, including 42,997 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 0.75 (42997 hom., cov: 33)
• Consequence: MAP1B NM_005909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 15 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 9

  Inheritance: AD Classification: STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1B	NM_005909.5	MANE Select	c.185-1169G>C		intron	N/A	NP_005900.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1B	ENST00000296755.12	TSL:1 MANE Select	c.185-1169G>C		intron	N/A	ENSP00000296755.7
	MAP1B	ENST00000511641.2	TSL:1	c.185-1169G>C		intron	N/A	ENSP00000423444.2
	MAP1B	ENST00000512974.5	TSL:4	c.185-1169G>C		intron	N/A	ENSP00000426312.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114096 AN: 152108 Hom.: 42945 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.750 AC: 114212 AN: 152226 Hom.: 42997 Cov.: 33 AF XY: 0.748 AC XY: 55667 AN XY: 74440

African (AFR) AF: 0.821 AC: 34108 AN: 41536

American (AMR) AF: 0.728 AC: 11146 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2676 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2897 AN: 5174

South Asian (SAS) AF: 0.696 AC: 3362 AN: 4828

European-Finnish (FIN) AF: 0.739 AC: 7835 AN: 10600

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49611 AN: 67996

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.718 Hom.: 19138

Bravo AF: 0.752

Asia WGS AF: 0.658 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		-0.81
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: rs2199161; hg19: chr5-71410356;