Genetic Variant CAMLG:c.*195T>G (chr5-134751145-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001745.4(CAMLG):c.*195T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 500,656 control chromosomes in the GnomAD database, including 17 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 0.0049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 16 hom. )

Consequence

CAMLG
NM_001745.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

CAMLG (HGNC:1471): (calcium modulating ligand) The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin B, cyclosporin A binds and inactivates the key signaling intermediate calcineurin. The protein encoded by this gene functions similarly to cyclosporin A, binding to cyclophilin B and acting downstream of the TCR and upstream of calcineurin by causing an influx of calcium. This integral membrane protein appears to be a new participant in the calcium signal transduction pathway, implicating cyclophilin B in calcium signaling, even in the absence of cyclosporin. [provided by RefSeq, Jul 2008]

CAMLG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMLG	NM_001745.4 link	c.*195T>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000297156.4	NP_001736.1	P49069
CAMLG	XM_047417791.1 link	c.*195T>G		3_prime_UTR_variant	Exon 3 of 3		XP_047273747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMLG	ENST00000297156.4 link	c.*195T>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001745.4	ENSP00000297156.2		P49069

Frequencies

GnomAD3 genomes

AF:

0.00489

AC:

745

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00798

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.00654

AC:

2278

AN:

348318

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

1193

AN XY:

180306

show subpopulations

African (AFR)

AF:

0.00208

AC:

AN:

11056

American (AMR)

AF:

0.00439

AC:

AN:

13886

Ashkenazi Jewish (ASJ)

AF:

0.000438

AC:

AN:

11414

East Asian (EAS)

AF:

0.0000357

AC:

AN:

28042

South Asian (SAS)

AF:

0.0104

AC:

248

AN:

23844

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

22578

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

1596

European-Non Finnish (NFE)

AF:

0.00809

AC:

1738

AN:

214744

Other (OTH)

AF:

0.00600

AC:

127

AN:

21158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00488

AC:

744

AN:

152338

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

337

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41586

American (AMR)

AF:

0.00465

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0101

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00798

AC:

543

AN:

68034

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00504

Hom.:

Bravo

AF:

0.00509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.84

Mutation Taster

=100/0

polymorphism

(source)

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

Below is the list of publications found by LitVar. It may be empty.

chr5-134751145-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over