15-57550243-G-A

Variant names:

• chr15-57550243-G-A
• rs11856
• NM_032866.5:c.*2753G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	NM_032866.5	MANE Select	c.*2753G>A		3_prime_UTR	Exon 19 of 19	NP_116255.2
	CGNL1	NM_001252335.2		c.*2753G>A		3_prime_UTR	Exon 20 of 20	NP_001239264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGNL1	ENST00000281282.6	TSL:1 MANE Select	c.*2753G>A		3_prime_UTR	Exon 19 of 19	ENSP00000281282.5

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.164 AC: 47 AN: 286

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.185 AC: 7694 AN: 41504

American (AMR) AF: 0.230 AC: 3512 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.125 AC: 647 AN: 5168

South Asian (SAS) AF: 0.194 AC: 934 AN: 4804

European-Finnish (FIN) AF: 0.201 AC: 2123 AN: 10564

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14317 AN: 68000

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.205 Hom.: 1987

Bravo AF: 0.203

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.49
PhyloP100		-4.7
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: rs11856; hg19: chr15-57842441;