dbSNP rs1957949: MAX:c.*587G>A (chr14-65075889-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0550

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MAX	NM_002382.5 link	c.*587G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000358664.9	NP_002373.3	P61244-1Q8TAX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAX	ENST00000358664 link	c.*587G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_002382.5	ENSP00000351490.4		P61244-1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78714

AN:

151668

Hom.:

23289

Cov.:

show subpopulations

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.:

AF XY:

0.430

AC XY:

181834

AN XY:

422524

show subpopulations

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.:

AF XY:

0.515

AC XY:

38203

AN XY:

74158

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pheochromocytoma

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over