rs45440292

Variant names:

• chr14-65076071-C-A
• rs45440292
• ENST00000394606.6:n.*661G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-65076071-C-A
• chr14-65076071-C-G
• chr14-65076071-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000394606.6(MAX):​n.*661G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000936 in 1,068,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: MAX ENST00000394606.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 0 publications found

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]

MAX Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• pheochromocytoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• polydactyly-macrocephaly syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAX	NM_002382.5	c.*405G>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000358664.9	NP_002373.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAX	ENST00000358664.9	c.*405G>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_002382.5	ENSP00000351490.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.36e-7 AC: 1 AN: 1068658 Hom.: 0 Cov.: 34 AF XY: 0.00000198 AC XY: 1 AN XY: 505004

African (AFR) AF: 0.00 AC: 0 AN: 23914

American (AMR) AF: 0.00 AC: 0 AN: 9204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14082

East Asian (EAS) AF: 0.00 AC: 0 AN: 21646

South Asian (SAS) AF: 0.0000266 AC: 1 AN: 37562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 908020

Other (OTH) AF: 0.00 AC: 0 AN: 42174

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.69
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs45440292; hg19: chr14-65542789;