NM_002382.5:c.64-3289G>A

Variant names:

• chr14-65097104-C-T
• rs1256415
• NM_002382.5:c.64-3289G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002382.5(MAX):​c.64-3289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,244 control chromosomes in the GnomAD database, including 1,809 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 0.10 (1809 hom., cov: 33)
• Consequence: MAX NM_002382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

Genes affected

MAX (HGNC:6913): (MYC associated factor X) The protein encoded by this gene is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxi1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Mutations of this gene have been reported to be associated with hereditary pheochromocytoma. A pseudogene of this gene is located on the long arm of chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAX	NM_002382.5	c.64-3289G>A		intron_variant	Intron 2 of 4	ENST00000358664.9	NP_002373.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAX	ENST00000358664.9	c.64-3289G>A		intron_variant	Intron 2 of 4	1	NM_002382.5	ENSP00000351490.4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15692 AN: 152126 Hom.: 1809 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.103 AC: 15706 AN: 152244 Hom.: 1809 Cov.: 33 AF XY: 0.103 AC XY: 7644 AN XY: 74462

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.0551 Hom.: 215

Bravo AF: 0.114

Asia WGS AF: 0.180 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.60

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: rs1256415; hg19: chr14-65563822;