14-65006156-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002028.4(FNTB):c.209+1860dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (13303 hom., cov: 0)
  • Exomes 𝑓: 0.23 (139 hom.)
  • Failed GnomAD Quality Control
• Consequence: FNTB NM_002028.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.672

Genes affected

FNTB (HGNC:3785): (farnesyltransferase, CAAX box, beta) Enables zinc ion binding activity. Contributes to protein farnesyltransferase activity. Involved in protein farnesylation. Part of microtubule associated complex and protein farnesyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

CHURC1-FNTB (HGNC:):

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 -10 ACMG points.

• BP6: Variant 14-65006156-C-CT is Benign according to our data. Variant chr14-65006156-C-CT is described in ClinVar as [Benign]. Clinvar id is 1233463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNTB	NM_002028.4	c.209+1860dup		intron_variant		ENST00000246166.3
CHURC1-FNTB	NM_001202559.1	c.392+1860dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNTB	ENST00000246166.3	c.209+1860dup		intron_variant		1	NM_002028.4	P1
FNTB	ENST00000555372.5	n.268+1860dup		intron_variant, non_coding_transcript_variant		3
FNTB	ENST00000555742.5	n.413+1860dup		intron_variant, non_coding_transcript_variant		5
MAX	ENST00000341653.6			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 58237 AN: 133380 Hom.: 13302 Cov.: 0

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.408

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.228 AC: 306655 AN: 1342652 Hom.: 139 Cov.: 0 AF XY: 0.223 AC XY: 149296 AN XY: 668528

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.437 AC: 58229 AN: 133354 Hom.: 13303 Cov.: 0 AF XY: 0.437 AC XY: 27860 AN XY: 63772

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.407

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs367570902; hg19: chr14-65472874;