Variant 6-7356075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170692.2(CAGE1):c.2248A>G(p.Ile750Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,550,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

CAGE1 (HGNC:21622): (cancer antigen 1)

CAGE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08780089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2 linkuse as main transcript	c.2248A>G	p.Ile750Val	missense_variant	10/14	ENST00000502583.6	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2 linkuse as main transcript	c.2194-964A>G		intron_variant			NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3 linkuse as main transcript	c.1705-964A>G		intron_variant			NP_995586.1	Q8TC20-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAGE1	ENST00000502583.6 linkuse as main transcript	c.2248A>G	p.Ile750Val	missense_variant	10/14	5	NM_001170692.2	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000379918.8 linkuse as main transcript	c.2182A>G	p.Ile728Val	missense_variant	10/14	5		ENSP00000369250.4	E7EUJ7
CAGE1	ENST00000338150.8 linkuse as main transcript	c.2194-964A>G		intron_variant		2		ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000512086.5 linkuse as main transcript	c.2113-964A>G		intron_variant		5		ENSP00000427583.1	Q8TC20-1
CAGE1	ENST00000296742.11 linkuse as main transcript	c.1705-964A>G		intron_variant		1		ENSP00000296742.7	Q8TC20-2
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1514A>G		non_coding_transcript_exon_variant	10/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*200A>G		non_coding_transcript_exon_variant	10/14	1		ENSP00000390644.2	Q8TC20-4
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1514A>G		3_prime_UTR_variant	10/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*200A>G		3_prime_UTR_variant	10/14	1		ENSP00000390644.2	Q8TC20-4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000641

AC:

AN:

156060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000808

AC:

113

AN:

1398524

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

689838

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000575

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000392

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.2248A>G (p.I750V) alteration is located in exon 10 (coding exon 9) of the CAGE1 gene. This alteration results from a A to G substitution at nucleotide position 2248, causing the isoleucine (I) at amino acid position 750 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.69

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.030

Sift

Benign

0.069

T;T

Sift4G

Benign

0.52

T;T

Vest4

0.12

MutPred

0.39

.;Loss of ubiquitination at K755 (P = 0.1278);

MVP

0.37

MPC

0.072

ClinPred

0.064

GERP RS

3.3

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over