dbSNP rs11158569: CHURC1:c.*1121C>T (chr14-64933351-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.*1121C>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 0.213 in 983,474 control chromosomes in the GnomAD database, including 23,993 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 ( 6084 hom., cov: 32)

Exomes 𝑓: 0.20 ( 17909 hom. )

Consequence

CHURC1
NM_001386928.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.583

Publications

12 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHURC1	NM_001386928.1 link	c.*1121C>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.*1121C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_001386928.1	ENSP00000448050.2		Q8WUH1-4
CHURC1-FNTB	ENST00000549987.1 link	c.246+7271C>T		intron_variant	Intron 3 of 13	2		ENSP00000447121.2		B4DL54

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40151

AN:

151952

Hom.:

6059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.204

AC:

169618

AN:

831404

Hom.:

17909

Cov.:

AF XY:

0.205

AC XY:

78699

AN XY:

384034

show subpopulations

African (AFR)

AF:

0.422

AC:

6638

AN:

15744

American (AMR)

AF:

0.205

AC:

201

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1554

AN:

5140

East Asian (EAS)

AF:

0.122

AC:

441

AN:

3612

South Asian (SAS)

AF:

0.287

AC:

4702

AN:

16408

European-Finnish (FIN)

AF:

0.237

AC:

114

AN:

482

Middle Eastern (MID)

AF:

0.235

AC:

379

AN:

1616

European-Non Finnish (NFE)

AF:

0.197

AC:

149598

AN:

760168

Other (OTH)

AF:

0.220

AC:

5991

AN:

27252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6736

13473

20209

26946

33682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7306

14612

21918

29224

36530

<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:

0.265

AC:

40239

AN:

152070

Hom.:

6084

Cov.:

AF XY:

0.266

AC XY:

19784

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.405

AC:

16789

AN:

41482

American (AMR)

AF:

0.205

AC:

3129

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3466

East Asian (EAS)

AF:

0.130

AC:

673

AN:

5180

South Asian (SAS)

AF:

0.292

AC:

1411

AN:

4824

European-Finnish (FIN)

AF:

0.232

AC:

2448

AN:

10564

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13825

AN:

67962

Other (OTH)

AF:

0.240

AC:

507

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1509

3019

4528

6038

7547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.273

Hom.:

3175

Bravo

AF:

0.270

Asia WGS

AF:

0.259

AC:

900

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.44

PhyloP100

-0.58

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