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 ENST00000549987.1(CHURC1-FNTB):c.246+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
ENST00000549987.1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHURC1-FNTB	NM_001202559.1 link	c.327+17749C>T		intron_variant	Intron 3 of 13		NP_001189488.1	B4DL54
CHURC1-FNTB	NM_001202558.2 link	c.6+19703C>T		intron_variant	Intron 2 of 12		NP_001189487.1	P49356-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1-FNTB	ENST00000549987.1 link	c.246+17749C>T		intron_variant	Intron 3 of 13	2		ENSP00000447121.2		B4DL54

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over