chr15-57470595-C-T

Position:

• chr15-57470595-C-T

Variant summary

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

The ENST00000281282.6(CGNL1):​c.2403+8703C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,210 control chromosomes in the GnomAD database, including 54,618 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 0.84 (54618 hom., cov: 32)
• Consequence: CGNL1 ENST00000281282.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGNL1	NM_032866.5	c.2403+8703C>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+8703C>T		intron_variant		1	NM_032866.5	ENSP00000281282	P1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128493 AN: 152092 Hom.: 54558 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.845 AC: 128613 AN: 152210 Hom.: 54618 Cov.: 32 AF XY: 0.849 AC XY: 63183 AN XY: 74412

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.827

Alfa AF: 0.798 Hom.: 104423

Bravo AF: 0.842

Asia WGS AF: 0.894 AC: 3108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.11

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: rs2934442; hg19: chr15-57762793;