dbSNP rs12440459: CGNL1:c.-16+26173C>T (chr15-57402740-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_032866.5(CGNL1):c.-16+26173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,218 control chromosomes in the GnomAD database, including 792 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 0.095 ( 792 hom., cov: 32)

Exomes 𝑓: 0.059 ( 0 hom. )

Consequence

CGNL1
NM_032866.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

Publications

1 publications found

Variant links:

Genes affected

CGNL1 (HGNC:25931): (cingulin like 1) This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

CGNL1 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGNL1	NM_032866.5 link	c.-16+26173C>T		intron_variant	Intron 1 of 18	ENST00000281282.6	NP_116255.2	Q0VF96-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CGNL1	ENST00000281282.6 link	c.-16+26173C>T	intron_variant	Intron 1 of 18	1	NM_032866.5	ENSP00000281282.5	Q0VF96-1
CGNL1	ENST00000557813.2 link	n.506+26C>T	intron_variant	Intron 6 of 7	1
CGNL1	ENST00000559194.1 link	n.544+25575C>T	intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0949

AC:

14428

AN:

152066

Hom.:

789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0711

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0916

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.0588

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0769

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0949

AC:

14447

AN:

152184

Hom.:

792

Cov.:

AF XY:

0.0985

AC XY:

7331

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0806

AC:

3348

AN:

41526

American (AMR)

AF:

0.134

AC:

2042

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

247

AN:

3472

East Asian (EAS)

AF:

0.0427

AC:

221

AN:

5180

South Asian (SAS)

AF:

0.152

AC:

730

AN:

4810

European-Finnish (FIN)

AF:

0.121

AC:

1283

AN:

10584

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0916

AC:

6232

AN:

68010

Other (OTH)

AF:

0.111

AC:

234

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

670

1340

2011

2681

3351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0926

Hom.:

1703

Bravo

AF:

0.0959

Asia WGS

AF:

0.116

AC:

405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

(source)

DANN

Benign

0.39

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over