rs4902359

Variant names:

• chr14-65076072-G-A
• rs4902359
• ENST00000394606.6:n.*660C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-65076072-G-A
• chr14-65076072-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000394606.6(MAX):​n.*660C>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 0.406 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 ENST00000394606.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41
• Publications: 18 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: Benign. The variant received -20 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 VariationId is 313807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394606.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAX	NM_002382.5	MANE Select	c.*404C>T		3_prime_UTR	Exon 5 of 5	NP_002373.3
	MAX	NR_073137.2		n.1011C>T		non_coding_transcript_exon	Exon 4 of 4
	MAX	NR_176275.1		n.1130C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAX	ENST00000394606.6	TSL:1	n.*660C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000378104.2
	MAX	ENST00000358664.9	TSL:1 MANE Select	c.*404C>T		3_prime_UTR	Exon 5 of 5	ENSP00000351490.4
	MAX	ENST00000358402.8	TSL:1	c.*404C>T		3_prime_UTR	Exon 4 of 4	ENSP00000351175.4

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

African (AFR) AF: 0.793 AC: 18813 AN: 23736

American (AMR) AF: 0.264 AC: 2416 AN: 9154

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 4030 AN: 13928

East Asian (EAS) AF: 0.472 AC: 10122 AN: 21432

South Asian (SAS) AF: 0.477 AC: 17399 AN: 36454

European-Finnish (FIN) AF: 0.402 AC: 3598 AN: 8954

Middle Eastern (MID) AF: 0.336 AC: 898 AN: 2676

European-Non Finnish (NFE) AF: 0.382 AC: 345521 AN: 904406

Other (OTH) AF: 0.408 AC: 17083 AN: 41828

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

African (AFR) AF: 0.768 AC: 31906 AN: 41534

American (AMR) AF: 0.306 AC: 4675 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2153 AN: 5156

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4820

European-Finnish (FIN) AF: 0.422 AC: 4455 AN: 10554

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25018 AN: 67966

Other (OTH) AF: 0.423 AC: 893 AN: 2112

Alfa AF: 0.401 Hom.: 48573

Bravo AF: 0.479

Asia WGS AF: 0.466 AC: 1618 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Pheochromocytoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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