rs45440292

chr14-65076071-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002382.5(MAX):c.*405G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,220,868 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (6 hom., cov: 33)
  • Exomes 𝑓: 0.012 (77 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.91

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=-0.9).
• BP6: Variant 14-65076071-C-T is Benign according to our data. Variant chr14-65076071-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 313806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00803 (1223/152246) while in subpopulation NFE AF= 0.013 (884/68008). AF 95% confidence interval is 0.0123. There are 6 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAX	NM_002382.5	c.*405G>A		3_prime_UTR_variant	5/5	ENST00000358664.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAX	ENST00000358664.9	c.*405G>A		3_prime_UTR_variant	5/5	1	NM_002382.5	P4

Frequencies

GnomAD3 genomes AF: 0.00805 AC: 1224 AN: 152130 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.0116 AC: 12429 AN: 1068622 Hom.: 77 Cov.: 34 AF XY: 0.0115 AC XY: 5813 AN XY: 504986

Gnomad4 AFR exome AF: 0.00222

Gnomad4 AMR exome AF: 0.00424

Gnomad4 ASJ exome AF: 0.000639

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00570

Gnomad4 FIN exome AF: 0.00929

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.00803 AC: 1223 AN: 152246 Hom.: 6 Cov.: 33 AF XY: 0.00768 AC XY: 572 AN XY: 74460

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00870 Hom.: 1

Bravo AF: 0.00746

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pheochromocytoma Benign:1

Likely 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	-0.90
Cadd	Benign	1.8
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: rs45440292; hg19: chr14-65542789;