15-57475784-G-T

Position:

• chr15-57475784-G-T

Variant summary

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

The NM_032866.5(CGNL1):​c.2403+13892G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 151,856 control chromosomes in the GnomAD database, including 49,703 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 0.81 (49703 hom., cov: 29)
• Consequence: CGNL1 NM_032866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGNL1	NM_032866.5	c.2403+13892G>T		intron_variant		ENST00000281282.6	NP_116255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGNL1	ENST00000281282.6	c.2403+13892G>T		intron_variant		1	NM_032866.5	ENSP00000281282.5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122509 AN: 151738 Hom.: 49675 Cov.: 29

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.807 AC: 122591 AN: 151856 Hom.: 49703 Cov.: 29 AF XY: 0.807 AC XY: 59912 AN XY: 74218

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.802

Alfa AF: 0.822 Hom.: 66733

Bravo AF: 0.801

Asia WGS AF: 0.671 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.21
DANN	Benign	0.49

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: rs2922219; hg19: chr15-57767982;