15-57438232-C-T

Variant names:

• chr15-57438232-C-T
• rs565854948
• NM_032866.5:c.233C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032866.5(CGNL1):​c.233C>T​(p.Pro78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,192 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P78H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (1 hom.)
• Consequence: CGNL1 NM_032866.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.101668596).

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.233C>T	p.Pro78Leu	missense	Exon 2 of 19	NP_116255.2
	CGNL1	NM_001252335.2		c.233C>T	p.Pro78Leu	missense	Exon 3 of 20	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.233C>T	p.Pro78Leu	missense	Exon 2 of 19	ENSP00000281282.5	Q0VF96-1
	CGNL1	ENST00000955758.1		c.233C>T	p.Pro78Leu	missense	Exon 2 of 20	ENSP00000625817.1
	CGNL1	ENST00000860577.1		c.233C>T	p.Pro78Leu	missense	Exon 2 of 19	ENSP00000530636.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251486 AF XY: 0.00

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461884 Hom.: 1 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 727248

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112002

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74472

African (AFR) AF: 0.000120 AC: 5 AN: 41566

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.44
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.20
Sift	Benign	0.10	T
Sift4G	Benign	0.30	T
Polyphen		0.047	B
Vest4		0.26
MutPred		0.25		Gain of sheet (P = 0.0125)
MVP		0.56
MPC		0.020
ClinPred		0.060	T
GERP RS		4.8
Varity_R		0.045
gMVP		0.52
Mutation Taster		=99/1	polymorphism

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: rs565854948; hg19: chr15-57730430; COSMIC: COSV107262723; COSMIC: COSV107262723;