3-47986654-T-A

Variant names:

• chr3-47986654-T-A
• rs13074973
• NM_001385682.1:c.224-8721A>T

Variant summary

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

The NM_001385682.1(MAP4):​c.224-8721A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,008 control chromosomes in the GnomAD database, including 29,070 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 0.60 (29070 hom., cov: 31)
• Consequence: MAP4 NM_001385682.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 7 publications found

Genes affected

MAP4 (HGNC:6862): (microtubule associated protein 4) The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385682.1. 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
	MAP4	NM_001385682.1	MANE Select	c.224-8721A>T		intron	N/A	NP_001372611.1	A0A804HKE7
	MAP4	NM_001385687.1		c.274+729A>T		intron	N/A	NP_001372616.1
	MAP4	NM_001385689.1		c.274+729A>T		intron	N/A	NP_001372618.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4	ENST00000683076.1	MANE Select	c.224-8721A>T		intron	N/A	ENSP00000507895.1	A0A804HKE7
	MAP4	ENST00000360240.10	TSL:1	c.224-8721A>T		intron	N/A	ENSP00000353375.6	P27816-1
	MAP4	ENST00000439356.2	TSL:1	c.224-8721A>T		intron	N/A	ENSP00000397414.1	P27816-7

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91913 AN: 151890 Hom.: 29068 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.605 AC: 91952 AN: 152008 Hom.: 29070 Cov.: 31 AF XY: 0.610 AC XY: 45317 AN XY: 74290

African (AFR) AF: 0.408 AC: 16893 AN: 41434

American (AMR) AF: 0.602 AC: 9182 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3744 AN: 5176

South Asian (SAS) AF: 0.634 AC: 3057 AN: 4822

European-Finnish (FIN) AF: 0.762 AC: 8047 AN: 10560

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46806 AN: 67972

Other (OTH) AF: 0.594 AC: 1253 AN: 2108

Alfa AF: 0.641 Hom.: 4000

Bravo AF: 0.584

Asia WGS AF: 0.637 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		1.5
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: rs13074973; hg19: chr3-48028144;