rs12440459

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
CGNL1NM_032866.5 linkuse as main transcriptc.-16+26173C>T intron_variant ENST00000281282.6 NP_116255.2 Q0VF96-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CGNL1ENST00000281282.6 linkuse as main transcriptc.-16+26173C>T intron_variant 1 NM_032866.5 ENSP00000281282.5 Q0VF96-1
CGNL1ENST00000557813.2 linkuse as main transcriptn.506+26C>T intron_variant 1
CGNL1ENST00000559194.1 linkuse as main transcriptn.544+25575C>T intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0949
AC:
14428
AN:
152066
Hom.:
789
Cov.:
32
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:
2
AN:
34
Hom.:
0
Cov.:
0
AF XY:
0.0769
AC XY:
2
AN XY:
26
show subpopulations
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.250
GnomAD4 genome
AF:
0.0949
AC:
14447
AN:
152184
Hom.:
792
Cov.:
32
AF XY:
0.0985
AC XY:
7331
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0806
Gnomad4 AMR
AF:
0.134
Gnomad4 ASJ
AF:
0.0711
Gnomad4 EAS
AF:
0.0427
Gnomad4 SAS
AF:
0.152
Gnomad4 FIN
AF:
0.121
Gnomad4 NFE
AF:
0.0916
Gnomad4 OTH
AF:
0.111
Alfa
AF:
0.0931
Hom.:
617
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
DANN
Benign
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12440459; hg19: chr15-57694938; API