rs4466998

chr14-65008822-C-Achr14-65008822-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002028.4(FNTB):c.210-3495C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,046 control chromosomes in the GnomAD database, including 23,736 homozygotes. 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: 𝑓 0.55 (23736 hom., cov: 32)
• Consequence: FNTB NM_002028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNTB	NM_002028.4	c.210-3495C>A		intron_variant		ENST00000246166.3
CHURC1-FNTB	NM_001202559.1	c.393-3495C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNTB	ENST00000246166.3	c.210-3495C>A		intron_variant		1	NM_002028.4	P1
MAX	ENST00000341653.6	c.172-2538G>T		intron_variant		2
FNTB	ENST00000555372.5	n.269-3495C>A		intron_variant, non_coding_transcript_variant		3
FNTB	ENST00000555742.5	n.414-3495C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83921 AN: 151930 Hom.: 23686 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 84042 AN: 152046 Hom.: 23736 Cov.: 32 AF XY: 0.554 AC XY: 41165 AN XY: 74310

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.506

Alfa AF: 0.494 Hom.: 22266

Bravo AF: 0.560

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.52
Dann	Benign	0.43

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: rs4466998; hg19: chr14-65475540;