14-65075349-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002382.5(MAX):c.*1127G>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 0.408 in 1,062,706 control chromosomes in the GnomAD database, including 93,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (20219 hom., cov: 32)
  • Exomes 𝑓: 0.40 (73704 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67

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=-0.38).
• BP6: Variant 14-65075349-C-G is Benign according to our data. Variant chr14-65075349-C-G is described in ClinVar as [Benign]. Clinvar id is 313793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAX	NM_002382.5	c.*1127G>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.*1127G>C		3_prime_UTR_variant	5/5	1	NM_002382.5	P4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73014 AN: 151898 Hom.: 20175 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.396 AC: 360992 AN: 910690 Hom.: 73704 Cov.: 33 AF XY: 0.396 AC XY: 166399 AN XY: 420524

Gnomad4 AFR exome AF: 0.804

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.481 AC: 73106 AN: 152016 Hom.: 20219 Cov.: 32 AF XY: 0.479 AC XY: 35567 AN XY: 74278

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.424

Alfa AF: 0.425 Hom.: 1924

Bravo AF: 0.480

Asia WGS AF: 0.467 AC: 1625 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	-0.38
Cadd	Benign	15
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4902357; hg19: chr14-65542067; COSMIC: COSV52418307; COSMIC: COSV52418307;