chr15-57402740-C-T

Variant names:

• chr15-57402740-C-T
• rs12440459
• NM_032866.5:c.-16+26173C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 1 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	NM_032866.5	MANE Select	c.-16+26173C>T		intron	N/A	NP_116255.2
	CGNL1	NM_001252335.2		c.-130-18396C>T		intron	N/A	NP_001239264.1	Q0VF96-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	ENST00000281282.6	TSL:1 MANE Select	c.-16+26173C>T		intron	N/A	ENSP00000281282.5	Q0VF96-1
	CGNL1	ENST00000557813.2	TSL:1	n.506+26C>T		intron	N/A
	CGNL1	ENST00000955758.1		c.-16+26173C>T		intron	N/A	ENSP00000625817.1

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14428 AN: 152066 Hom.: 789 Cov.: 32

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0949 AC: 14447 AN: 152184 Hom.: 792 Cov.: 32 AF XY: 0.0985 AC XY: 7331 AN XY: 74398

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: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6232 AN: 68010

Other (OTH) AF: 0.111 AC: 234 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12440459; hg19: chr15-57694938;