14-65075759-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002382.5(MAX):c.*717T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,065,706 control chromosomes in the GnomAD database, including 60,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6157 hom., cov: 32)
  • Exomes 𝑓: 0.34 (54343 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-65075759-A-G is Benign according to our data. Variant chr14-65075759-A-G is described in ClinVar as [Benign]. Clinvar id is 313798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAX	NM_002382.5	c.*717T>C		3_prime_UTR_variant	5/5	ENST00000358664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAX	ENST00000358664.9	c.*717T>C		3_prime_UTR_variant	5/5	1	NM_002382.5	P4

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41081 AN: 151906 Hom.: 6161 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.342 AC: 312501 AN: 913682 Hom.: 54343 Cov.: 33 AF XY: 0.343 AC XY: 144495 AN XY: 421856

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.270 AC: 41082 AN: 152024 Hom.: 6157 Cov.: 32 AF XY: 0.271 AC XY: 20113 AN XY: 74312

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.239

Alfa AF: 0.309 Hom.: 7580

Bravo AF: 0.249

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pheochromocytoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.22
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs4902358; hg19: chr14-65542477;