Genetic Variant CHURC1-FNTB:c.246+19643T>C (chr14-64945723-T-C) – 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+19643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,500 control chromosomes in the GnomAD database, including 11,435 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 0.38 ( 11410 hom., cov: 32)

Exomes 𝑓: 0.36 ( 25 hom. )

Consequence

CHURC1-FNTB
ENST00000549987.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.148

Publications

16 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:

RAB15 (HGNC:20150): (RAB15, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in positive regulation of regulated secretory pathway. Located in cilium; endosome membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB15 links:

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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 (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB15	NM_001308154.2 link	c.*2631A>G		downstream_gene_variant		ENST00000533601.7	NP_001295083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1-FNTB	ENST00000549987.1 link	c.246+19643T>C		intron_variant	Intron 3 of 13	2		ENSP00000447121.2
RAB15	ENST00000533601.7 link	c.*2631A>G		downstream_gene_variant		1	NM_001308154.2	ENSP00000434103.3

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57359

AN:

151920

Hom.:

11391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.359

AC:

166

AN:

462

Hom.:

AF XY:

0.421

AC XY:

118

AN XY:

280

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.362

AC:

129

AN:

356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.341

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.378

AC:

57422

AN:

152038

Hom.:

11410

Cov.:

AF XY:

0.381

AC XY:

28320

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.434

AC:

17990

AN:

41454

American (AMR)

AF:

0.301

AC:

4591

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1358

AN:

3466

East Asian (EAS)

AF:

0.699

AC:

3608

AN:

5160

South Asian (SAS)

AF:

0.384

AC:

1852

AN:

4822

European-Finnish (FIN)

AF:

0.378

AC:

3997

AN:

10576

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22728

AN:

67974

Other (OTH)

AF:

0.367

AC:

774

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1763

3527

5290

7054

8817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.348

Hom.:

3382

Bravo

AF:

0.380

Asia WGS

AF:

0.519

AC:

1805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.34

PhyloP100

-0.15

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