Genetic Variant COLCA1:n.4988C>A (chr11-111293999-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000355430.5(COLCA1):n.4988C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,204 control chromosomes in the GnomAD database, including 919 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 0.093 ( 918 hom., cov: 33)

Exomes 𝑓: 0.096 ( 1 hom. )

Consequence

COLCA1
ENST00000355430.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

Publications

3 publications found

Variant links:

Genes affected

COLCA1 (HGNC:33789): (colorectal cancer associated 1) This gene encodes a transmembrane protein that localizes to granular structures, including crystalloid eosinophilic granules and other granular organelles. This gene, along with an overlapping opposite strand gene, has been implicated as a susceptibility locus for colorectal cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

COLCA1 links:

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new If you want to explore the variant's impact on the transcript ENST00000355430.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355430.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
COLCA1	NR_169237.1	n.4889C>A	non_coding_transcript_exon	Exon 2 of 2
COLCA1	NR_169241.1	n.4756C>A	non_coding_transcript_exon	Exon 2 of 2
COLCA1	NR_169242.1	n.4792C>A	non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
COLCA1	ENST00000355430.5	TSL:1	n.4988C>A	non_coding_transcript_exon	Exon 2 of 2
COLCA1	ENST00000532918.4	TSL:1	n.4756C>A	non_coding_transcript_exon	Exon 2 of 2
COLCA1	ENST00000540738.3	TSL:1	n.4927C>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0929

AC:

14105

AN:

151888

Hom.:

919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.0458

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.0960

AC:

AN:

198

Hom.:

Cov.:

AF XY:

0.0917

AC XY:

AN XY:

120

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0960

AC:

AN:

198

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0927

AC:

14098

AN:

152006

Hom.:

918

Cov.:

AF XY:

0.0911

AC XY:

6769

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0234

AC:

971

AN:

41460

American (AMR)

AF:

0.126

AC:

1922

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

846

AN:

3472

East Asian (EAS)

AF:

0.00463

AC:

AN:

5186

South Asian (SAS)

AF:

0.0460

AC:

221

AN:

4802

European-Finnish (FIN)

AF:

0.0937

AC:

992

AN:

10590

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8631

AN:

67904

Other (OTH)

AF:

0.113

AC:

238

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

659

1319

1978

2638

3297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0982

Hom.:

455

Bravo

AF:

0.0937

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.32

(source)

DANN

Benign

0.57

PhyloP100

-0.0020

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over