rs1957949

chr14-65075889-C-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.*587G>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 0.444 in 1,066,874 control chromosomes in the GnomAD database, including 110,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (23346 hom., cov: 33)
  • Exomes 𝑓: 0.43 (87126 hom.)
• Consequence: MAX NM_002382.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

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=-0.83).
• BP6: Variant 14-65075889-C-T is Benign according to our data. Variant chr14-65075889-C-T is described in ClinVar as [Benign]. Clinvar id is 313801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAX	NM_002382.5	c.*587G>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.*587G>A		3_prime_UTR_variant	5/5	1	NM_002382.5	P4

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78714 AN: 151668 Hom.: 23289 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.431 AC: 394490 AN: 915086 Hom.: 87126 Cov.: 30 AF XY: 0.430 AC XY: 181834 AN XY: 422524

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.519 AC: 78824 AN: 151788 Hom.: 23346 Cov.: 33 AF XY: 0.515 AC XY: 38203 AN XY: 74158

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.468

Alfa AF: 0.434 Hom.: 4875

Bravo AF: 0.523

Asia WGS AF: 0.482 AC: 1678 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	-0.83
Cadd	Benign	7.5
Dann	Benign	0.65

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: rs1957949; hg19: chr14-65542607; COSMIC: COSV52420205; COSMIC: COSV52420205;