Genetic Variant CHURC1:c.*1317C>T (chr14-64933547-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_001386928.1(CHURC1):c.*1317C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 976,432 control chromosomes in the GnomAD database, including 60,765 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 0.47 ( 20400 hom., cov: 32)

Exomes 𝑓: 0.30 ( 40365 hom. )

Consequence

CHURC1
NM_001386928.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320

Publications

18 publications found

Variant links:

Genes affected

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:

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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHURC1	NM_001386928.1 link	c.*1317C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000549115.7	NP_001373857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1	ENST00000549115.7 link	c.*1317C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_001386928.1	ENSP00000448050.2		Q8WUH1-4
CHURC1-FNTB	ENST00000549987.1 link	c.246+7467C>T		intron_variant	Intron 3 of 13	2		ENSP00000447121.2		B4DL54

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70569

AN:

151866

Hom.:

20346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.714

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.300

AC:

247323

AN:

824448

Hom.:

40365

Cov.:

AF XY:

0.300

AC XY:

114139

AN XY:

381068

show subpopulations

African (AFR)

AF:

0.853

AC:

13269

AN:

15564

American (AMR)

AF:

0.369

AC:

362

AN:

980

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1982

AN:

5086

East Asian (EAS)

AF:

0.704

AC:

2519

AN:

3578

South Asian (SAS)

AF:

0.367

AC:

5981

AN:

16276

European-Finnish (FIN)

AF:

0.351

AC:

AN:

276

Middle Eastern (MID)

AF:

0.364

AC:

584

AN:

1604

European-Non Finnish (NFE)

AF:

0.283

AC:

213078

AN:

754118

Other (OTH)

AF:

0.350

AC:

9451

AN:

26966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

7935

15870

23806

31741

39676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9954

19908

29862

39816

49770

<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:

0.465

AC:

70685

AN:

151984

Hom.:

20400

Cov.:

AF XY:

0.467

AC XY:

34662

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.805

AC:

33418

AN:

41492

American (AMR)

AF:

0.365

AC:

5574

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1332

AN:

3466

East Asian (EAS)

AF:

0.714

AC:

3687

AN:

5166

South Asian (SAS)

AF:

0.393

AC:

1893

AN:

4822

European-Finnish (FIN)

AF:

0.355

AC:

3727

AN:

10500

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19637

AN:

67938

Other (OTH)

AF:

0.438

AC:

924

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1566

3132

4698

6264

7830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.371

Hom.:

24281

Bravo

AF:

0.488

Asia WGS

AF:

0.560

AC:

1946

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

(source)

DANN

Benign

0.53

PhyloP100

0.032

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