rs10518923

chr15-57494048-A-Cchr15-57494048-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032866.5(CGNL1):c.2404-22732A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,220 control chromosomes in the GnomAD database, including 2,426 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 0.16 (2426 hom., cov: 33)
• Consequence: CGNL1 NM_032866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGNL1	NM_032866.5	c.2404-22732A>C		intron_variant		ENST00000281282.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGNL1	ENST00000281282.6	c.2404-22732A>C		intron_variant		1	NM_032866.5	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24735 AN: 152100 Hom.: 2427 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24741 AN: 152220 Hom.: 2426 Cov.: 33 AF XY: 0.170 AC XY: 12655 AN XY: 74424

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.164

Alfa AF: 0.127 Hom.: 887

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.3
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs10518923; hg19: chr15-57786246;