3-47873628-A-G

Variant names:

• chr3-47873628-A-G
• rs319682
• NM_001385682.1:c.5758-1528T>C

Variant summary

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

The NM_001385682.1(MAP4):​c.5758-1528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,114 control chromosomes in the GnomAD database, including 12,696 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 0.39 (12696 hom., cov: 32)
• Consequence: MAP4 NM_001385682.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1	c.5758-1528T>C		intron_variant	Intron 12 of 20	ENST00000683076.1	NP_001372611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4	ENST00000683076.1	c.5758-1528T>C		intron_variant	Intron 12 of 20		NM_001385682.1	ENSP00000507895.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58565 AN: 151996 Hom.: 12673 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.386 AC: 58646 AN: 152114 Hom.: 12696 Cov.: 32 AF XY: 0.380 AC XY: 28264 AN XY: 74350

African (AFR) AF: 0.593 AC: 24584 AN: 41484

American (AMR) AF: 0.385 AC: 5885 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5182

South Asian (SAS) AF: 0.367 AC: 1774 AN: 4828

European-Finnish (FIN) AF: 0.209 AC: 2210 AN: 10574

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20239 AN: 67970

Other (OTH) AF: 0.396 AC: 838 AN: 2114

Alfa AF: 0.361 Hom.: 5835

Bravo AF: 0.408

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.57
PhyloP100		-1.6
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: rs319682; hg19: chr3-47915118;