rs1280420

Variant names:

• chr15-57458588-A-G
• rs1280420
• NM_032866.5:c.2191-3092A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-57458588-A-G
• chr15-57458588-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032866.5(CGNL1):​c.2191-3092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 152,262 control chromosomes in the GnomAD database, including 72,456 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 0.97 (72456 hom., cov: 31)
• Consequence: CGNL1 NM_032866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.2191-3092A>G		intron	N/A	NP_116255.2
	CGNL1	NM_001252335.2		c.2191-3092A>G		intron	N/A	NP_001239264.1	Q0VF96-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	ENST00000281282.6	TSL:1 MANE Select	c.2191-3092A>G		intron	N/A	ENSP00000281282.5	Q0VF96-1
	CGNL1	ENST00000955758.1		c.2191-3092A>G		intron	N/A	ENSP00000625817.1
	CGNL1	ENST00000860577.1		c.2191-3092A>G		intron	N/A	ENSP00000530636.1

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148319 AN: 152144 Hom.: 72411 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.984

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

GnomAD4 genome AF: 0.975 AC: 148421 AN: 152262 Hom.: 72456 Cov.: 31 AF XY: 0.976 AC XY: 72647 AN XY: 74444

African (AFR) AF: 0.913 AC: 37919 AN: 41536

American (AMR) AF: 0.989 AC: 15122 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68011 AN: 68030

Other (OTH) AF: 0.984 AC: 2079 AN: 2112

Alfa AF: 0.984 Hom.: 10289

Bravo AF: 0.972

Asia WGS AF: 0.993 AC: 3454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.029
DANN	Benign	0.64
PhyloP100		-1.9
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: rs1280420; hg19: chr15-57750786;