rs4902359

chr14-65076072-G-Achr14-65076072-G-T

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.*404C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,214,674 control chromosomes in the GnomAD database, including 106,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (20060 hom., cov: 33)
  • Exomes 𝑓: 0.40 (86026 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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=-0.86).
• BP6: Variant 14-65076072-G-A is Benign according to our data. Variant chr14-65076072-G-A is described in ClinVar as [Benign]. Clinvar id is 313807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAX	NM_002382.5	c.*404C>T		3_prime_UTR_variant	5/5	ENST00000358664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAX	ENST00000358664.9	c.*404C>T		3_prime_UTR_variant	5/5	1	NM_002382.5	P4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72840 AN: 151990 Hom.: 20026 Cov.: 33

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.395 AC: 419880 AN: 1062568 Hom.: 86026 Cov.: 36 AF XY: 0.395 AC XY: 198221 AN XY: 501542

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.479 AC: 72919 AN: 152106 Hom.: 20060 Cov.: 33 AF XY: 0.478 AC XY: 35503 AN XY: 74344

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.423

Alfa AF: 0.375 Hom.: 18236

Bravo AF: 0.479

Asia WGS AF: 0.466 AC: 1618 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.1
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4902359; hg19: chr14-65542790; COSMIC: COSV52418312; COSMIC: COSV52418312;