Genetic Variant CHURC1-FNTB:c.246+17749C>T (chr14-64943829-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001202559.1(CHURC1-FNTB):c.327+17749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 153,522 control chromosomes in the GnomAD database, including 7,066 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 0.29 ( 7009 hom., cov: 32)

Exomes 𝑓: 0.22 ( 57 hom. )

Consequence

CHURC1-FNTB
NM_001202559.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

22 publications found

Variant links:

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-FNTB links:

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]

CHURC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 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+17749C>T		intron	N/A	NP_001189488.1	B4DL54
	CHURC1-FNTB	NM_001202558.2		c.6+19703C>T		intron	N/A	NP_001189487.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+17749C>T	intron	N/A	ENSP00000447121.2	B4DL54
CHURC1	ENST00000551093.6	TSL:2	c.*417C>T	3_prime_UTR	Exon 4 of 4	ENSP00000446610.2	B7Z3N2
CHURC1	ENST00000551947.6	TSL:2	c.*508C>T	3_prime_UTR	Exon 3 of 3	ENSP00000446697.2	H0YHB4

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43300

AN:

151922

Hom.:

6997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.221

AC:

328

AN:

1482

Hom.:

Cov.:

AF XY:

0.216

AC XY:

176

AN XY:

814

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.246

AC:

AN:

358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.600

AC:

AN:

South Asian (SAS)

AF:

0.171

AC:

AN:

140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.206

AC:

185

AN:

900

Other (OTH)

AF:

0.289

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.285

AC:

43347

AN:

152040

Hom.:

7009

Cov.:

AF XY:

0.288

AC XY:

21394

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.388

AC:

16088

AN:

41428

American (AMR)

AF:

0.209

AC:

3192

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

894

AN:

3464

East Asian (EAS)

AF:

0.620

AC:

3209

AN:

5172

South Asian (SAS)

AF:

0.245

AC:

1180

AN:

4814

European-Finnish (FIN)

AF:

0.310

AC:

3278

AN:

10566

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14728

AN:

68000

Other (OTH)

AF:

0.258

AC:

545

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1533

3066

4600

6133

7666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.221

Hom.:

5687

Bravo

AF:

0.287

Asia WGS

AF:

0.420

AC:

1461

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.69

(source)

DANN

Benign

0.88

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over