rs4902347

Variant names:

• chr14-64944482-C-T
• rs4902347
• ENST00000549987.1:c.246+18402C>T

Variant summary

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

The NM_001202559.1(CHURC1-FNTB):​c.327+18402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,268 control chromosomes in the GnomAD database, including 789 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 0.089 (786 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: CHURC1-FNTB NM_001202559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202559.1. 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+18402C>T		intron	N/A	NP_001189488.1
	CHURC1-FNTB	NM_001202558.2		c.6+20356C>T		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+18402C>T		intron	N/A	ENSP00000447121.2
	CHURC1	ENST00000551947.6	TSL:2	c.*1161C>T		3_prime_UTR	Exon 3 of 3	ENSP00000446697.2
	CHURC1-FNTB	ENST00000553743.5	TSL:2	c.91+20356C>T		intron	N/A	ENSP00000450692.1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13543 AN: 152058 Hom.: 785 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0731

GnomAD4 exome AF: 0.120 AC: 11 AN: 92 Hom.: 3 Cov.: 0 AF XY: 0.115 AC XY: 9 AN XY: 78

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.122 AC: 10 AN: 82

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0890 AC: 13546 AN: 152176 Hom.: 786 Cov.: 32 AF XY: 0.0905 AC XY: 6729 AN XY: 74394

African (AFR) AF: 0.0227 AC: 942 AN: 41554

American (AMR) AF: 0.0815 AC: 1246 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3472

East Asian (EAS) AF: 0.0706 AC: 365 AN: 5168

South Asian (SAS) AF: 0.0231 AC: 111 AN: 4814

European-Finnish (FIN) AF: 0.175 AC: 1852 AN: 10590

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8372 AN: 67978

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.104 Hom.: 111

Bravo AF: 0.0810

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		1.0
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: rs4902347; hg19: chr14-65411200;