14-65053272-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_002028.4(FNTB):c.990C>T(p.Phe330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,455,536 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (10 hom., cov: 32)
  • Exomes 𝑓: 0.014 (124 hom.)
• Consequence: FNTB NM_002028.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.347

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 14-65053272-C-T is Benign according to our data. Variant chr14-65053272-C-T is described in ClinVar as [Benign]. Clinvar id is 2644329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.347 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0138 (17999/1303190) while in subpopulation NFE AF= 0.0158 (16252/1026606). AF 95% confidence interval is 0.0156. There are 124 homozygotes in gnomad4_exome. There are 8671 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNTB	NM_002028.4	c.990C>T	p.Phe330=	synonymous_variant	10/12	ENST00000246166.3
CHURC1-FNTB	NM_001202559.1	c.1173C>T	p.Phe391=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNTB	ENST00000246166.3	c.990C>T	p.Phe330=	synonymous_variant	10/12	1	NM_002028.4	P1
MAX	ENST00000341653.6	c.171+40436G>A		intron_variant		2
FNTB	ENST00000554334.5	n.958C>T		non_coding_transcript_exon_variant	8/10	2
FNTB	ENST00000557300.1	n.113C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1300 AN: 152228 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00875 AC: 1458 AN: 166700 Hom.: 11 AF XY: 0.00914 AC XY: 832 AN XY: 91010

Gnomad AFR exome AF: 0.00189

Gnomad AMR exome AF: 0.00216

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.0000975

Gnomad SAS exome AF: 0.00744

Gnomad FIN exome AF: 0.00637

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.0138 AC: 17999 AN: 1303190 Hom.: 124 Cov.: 30 AF XY: 0.0135 AC XY: 8671 AN XY: 642576

Gnomad4 AFR exome AF: 0.00188

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.00347

Gnomad4 EAS exome AF: 0.0000926

Gnomad4 SAS exome AF: 0.00848

Gnomad4 FIN exome AF: 0.00635

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.00853 AC: 1300 AN: 152346 Hom.: 10 Cov.: 32 AF XY: 0.00784 AC XY: 584 AN XY: 74496

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0131 Hom.: 15

Bravo AF: 0.00806

Asia WGS AF: 0.00346 AC: 12 AN: 3478

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

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

CHURC1-FNTB: BP4, BP7, BS1, BS2; FNTB: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	7.5
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34156365; hg19: chr14-65519990;