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 NM_001202559.1(CHURC1-FNTB):c.327+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
NM_001202559.1 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHURC1-FNTB	NM_001202559.1		c.327+19643T>C	intron	N/A	NP_001189488.1	B4DL54
CHURC1-FNTB	NM_001202558.2		c.6+21597T>C	intron	N/A	NP_001189487.1
RAB15	NM_001308154.2	MANE Select	c.*2631A>G	downstream_gene	N/A	NP_001295083.1	G5EMR8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+19643T>C	intron	N/A	ENSP00000447121.2	B4DL54
CHURC1-FNTB	ENST00000553743.5	TSL:2	c.91+21597T>C	intron	N/A	ENSP00000450692.1	H0YJ25
CHURC1-FNTB	ENST00000551823.1	TSL:2	n.*62+13431T>C	intron	N/A	ENSP00000449709.1	H0YIM9

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over