rs2922220

Variant names:

• chr15-57476443-T-C
• rs2922220
• NM_032866.5:c.2403+14551T>C

Variant summary

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

The NM_032866.5(CGNL1):​c.2403+14551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,124 control chromosomes in the GnomAD database, including 14,614 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 0.43 (14614 hom., cov: 33)
• Consequence: CGNL1 NM_032866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGNL1	NM_032866.5	c.2403+14551T>C		intron_variant	Intron 8 of 18	ENST00000281282.6	NP_116255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGNL1	ENST00000281282.6	c.2403+14551T>C		intron_variant	Intron 8 of 18	1	NM_032866.5	ENSP00000281282.5

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65712 AN: 152006 Hom.: 14602 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.432 AC: 65753 AN: 152124 Hom.: 14614 Cov.: 33 AF XY: 0.425 AC XY: 31642 AN XY: 74378

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.418

Alfa AF: 0.463 Hom.: 22057

Bravo AF: 0.433

Asia WGS AF: 0.183 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.82

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: rs2922220; hg19: chr15-57768641;