14-65006156-C-CTT

Variant summary

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

The NM_002028.4(FNTB):c.209+1859_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 0.13 (1243 hom., cov: 0)
  • Exomes 𝑓: 0.069 (35 hom.)
• 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-CTT is Benign according to our data. Variant chr14-65006156-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1245444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNTB	NM_002028.4	c.209+1859_209+1860dup		intron_variant		ENST00000246166.3
CHURC1-FNTB	NM_001202559.1	c.392+1859_392+1860dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNTB	ENST00000246166.3	c.209+1859_209+1860dup		intron_variant		1	NM_002028.4	P1
FNTB	ENST00000555372.5	n.268+1859_268+1860dup		intron_variant, non_coding_transcript_variant		3
FNTB	ENST00000555742.5	n.413+1859_413+1860dup		intron_variant, non_coding_transcript_variant		5
MAX	ENST00000341653.6			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 17149 AN: 133352 Hom.: 1240 Cov.: 0

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.0688 AC: 91967 AN: 1336218 Hom.: 35 Cov.: 0 AF XY: 0.0669 AC XY: 44536 AN XY: 665586

Gnomad4 AFR exome AF: 0.0355

Gnomad4 AMR exome AF: 0.0640

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.0506

Gnomad4 SAS exome AF: 0.0430

Gnomad4 FIN exome AF: 0.0531

Gnomad4 NFE exome AF: 0.0748

Gnomad4 OTH exome AF: 0.0587

GnomAD4 genome AF: 0.129 AC: 17157 AN: 133324 Hom.: 1243 Cov.: 0 AF XY: 0.129 AC XY: 8225 AN XY: 63754

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.124

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 09, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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;