rs11856

chr15-57550243-G-Achr15-57550243-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.*2753G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,402 control chromosomes in the GnomAD database, including 3,085 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 0.20 (3078 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: CGNL1 NM_032866.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.70

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGNL1	NM_032866.5	c.*2753G>A		3_prime_UTR_variant	19/19	ENST00000281282.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGNL1	ENST00000281282.6	c.*2753G>A		3_prime_UTR_variant	19/19	1	NM_032866.5	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30368 AN: 151984 Hom.: 3068 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.171 AC: 51 AN: 298 Hom.: 7 Cov.: 0 AF XY: 0.188 AC XY: 33 AN XY: 176

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.200 AC: 30415 AN: 152104 Hom.: 3078 Cov.: 32 AF XY: 0.200 AC XY: 14875 AN XY: 74350

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.185

Alfa AF: 0.204 Hom.: 1794

Bravo AF: 0.203

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0040
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: rs11856; hg19: chr15-57842441;