rs319690

Variant names:

• chr3-47885994-T-C
• rs319690
• NM_001385682.1:c.5435-8471A>G

Variant summary

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

The NM_001385682.1(MAP4):​c.5435-8471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,046 control chromosomes in the GnomAD database, including 12,620 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 0.38 (12620 hom., cov: 32)
• Consequence: MAP4 NM_001385682.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 44 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1	c.5435-8471A>G		intron_variant	Intron 10 of 20	ENST00000683076.1	NP_001372611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4	ENST00000683076.1	c.5435-8471A>G		intron_variant	Intron 10 of 20		NM_001385682.1	ENSP00000507895.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58412 AN: 151928 Hom.: 12598 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.361

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: 0.385 AC: 58492 AN: 152046 Hom.: 12620 Cov.: 32 AF XY: 0.379 AC XY: 28195 AN XY: 74338

African (AFR) AF: 0.589 AC: 24433 AN: 41462

American (AMR) AF: 0.386 AC: 5898 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5162

South Asian (SAS) AF: 0.367 AC: 1772 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2214 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20230 AN: 67950

Other (OTH) AF: 0.397 AC: 839 AN: 2114

Alfa AF: 0.850 Hom.: 34164

Bravo AF: 0.407

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-1.1
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: rs319690; hg19: chr3-47927484;