5-72183772-G-A

Position:

• chr5-72183772-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005909.5(MAP1B):​c.316G>A​(p.Val106Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,614,094 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (2 hom.)
• Consequence: MAP1B NM_005909.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• PP2: Missense variant where missense usually causes diseases, MAP1B
• BP4: Computational evidence support a benign effect (MetaRNN=0.004737675).
• BP6: Variant 5-72183772-G-A is Benign according to our data. Variant chr5-72183772-G-A is described in ClinVar as [Benign]. Clinvar id is 710962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00383 (583/152296) while in subpopulation AFR AF= 0.013 (542/41570). AF 95% confidence interval is 0.0121. There are 1 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 583 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1B	NM_005909.5	c.316G>A	p.Val106Ile	missense_variant	3/7	ENST00000296755.12
MAP1B	NM_001324255.2	c.-63G>A		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP1B	ENST00000296755.12	c.316G>A	p.Val106Ile	missense_variant	3/7	1	NM_005909.5	P1

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 582 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000935 AC: 235 AN: 251394 Hom.: 2 AF XY: 0.000559 AC XY: 76 AN XY: 135874

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000470 AC: 687 AN: 1461798 Hom.: 2 Cov.: 30 AF XY: 0.000374 AC XY: 272 AN XY: 727200

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.00383 AC: 583 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74476

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000622 Hom.: 0

Bravo AF: 0.00401

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0118 AC: 52

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00128 AC: 156

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

MAP1B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.92
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.72
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.36	T;T;T
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.087	.;B;.
Vest4		0.14
MVP		0.41
MPC		0.69
ClinPred		0.0046	T
GERP RS		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.018
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs141301811; hg19: chr5-71479599;