rs2922220

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	NM_032866.5	MANE Select	c.2403+14551T>C		intron	N/A	NP_116255.2
	CGNL1	NM_001252335.2		c.2403+14551T>C		intron	N/A	NP_001239264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	ENST00000281282.6	TSL:1 MANE Select	c.2403+14551T>C		intron	N/A	ENSP00000281282.5
	CGNL1	ENST00000955758.1		c.2403+14551T>C		intron	N/A	ENSP00000625817.1
	CGNL1	ENST00000860577.1		c.2403+14551T>C		intron	N/A	ENSP00000530636.1

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

African (AFR) AF: 0.426 AC: 17669 AN: 41476

American (AMR) AF: 0.430 AC: 6574 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3470

East Asian (EAS) AF: 0.119 AC: 616 AN: 5184

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4822

European-Finnish (FIN) AF: 0.406 AC: 4295 AN: 10588

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32364 AN: 67974

Other (OTH) AF: 0.418 AC: 881 AN: 2110

Alfa AF: 0.463 Hom.: 26159

Bravo AF: 0.433

Asia WGS AF: 0.183 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.82
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2922220; hg19: chr15-57768641;