ENST00000549987.1:c.246+11644A>C

Variant names:

• chr14-64937724-A-C
• rs10133290
• ENST00000549987.1:c.246+11644A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549987.1(CHURC1-FNTB):​c.246+11644A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,134 control chromosomes in the GnomAD database, including 6,106 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 0.26 (6106 hom., cov: 32)
• Consequence: CHURC1-FNTB ENST00000549987.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 15 publications found

Genes affected

CHURC1-FNTB (HGNC:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

CHURC1 (HGNC:20099): (churchill domain containing 1) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549987.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHURC1-FNTB	NM_001202559.1		c.327+11644A>C		intron	N/A	NP_001189488.1
	CHURC1-FNTB	NM_001202558.2		c.6+13598A>C		intron	N/A	NP_001189487.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+11644A>C		intron	N/A	ENSP00000447121.2
	CHURC1	ENST00000551093.6	TSL:2	c.247-5575A>C		intron	N/A	ENSP00000446610.2
	CHURC1-FNTB	ENST00000553743.5	TSL:2	c.91+13598A>C		intron	N/A	ENSP00000450692.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40210 AN: 152016 Hom.: 6081 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.265 AC: 40298 AN: 152134 Hom.: 6106 Cov.: 32 AF XY: 0.266 AC XY: 19807 AN XY: 74378

African (AFR) AF: 0.406 AC: 16834 AN: 41466

American (AMR) AF: 0.205 AC: 3129 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.130 AC: 674 AN: 5178

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13837 AN: 68002

Other (OTH) AF: 0.241 AC: 510 AN: 2114

Alfa AF: 0.233 Hom.: 2377

Bravo AF: 0.270

Asia WGS AF: 0.259 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10133290; hg19: chr14-65404442;