Variant 6-7365571-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170692.2(CAGE1):c.2090T>C(p.Ile697Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,608,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017742813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2 linkuse as main transcript	c.2090T>C	p.Ile697Thr	missense_variant	9/14	ENST00000502583.6	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2 linkuse as main transcript	c.2090T>C	p.Ile697Thr	missense_variant	9/13		NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3 linkuse as main transcript	c.1601T>C	p.Ile534Thr	missense_variant	7/11		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.2090T>C	p.Ile697Thr	missense_variant	9/14	5	NM_001170692.2	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000338150.8 linkuse as main transcript	c.2090T>C	p.Ile697Thr	missense_variant	9/13	2		ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000379918.8 linkuse as main transcript	c.2024T>C	p.Ile675Thr	missense_variant	9/14	5		ENSP00000369250.4	E7EUJ7
CAGE1	ENST00000512086.5 linkuse as main transcript	c.2009T>C	p.Ile670Thr	missense_variant	8/12	5		ENSP00000427583.1	Q8TC20-1
CAGE1	ENST00000296742.11 linkuse as main transcript	c.1601T>C	p.Ile534Thr	missense_variant	7/11	1		ENSP00000296742.7	Q8TC20-2
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1356T>C		non_coding_transcript_exon_variant	9/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*42T>C		non_coding_transcript_exon_variant	9/14	1		ENSP00000390644.2	Q8TC20-4
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1356T>C		3_prime_UTR_variant	9/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*42T>C		3_prime_UTR_variant	9/14	1		ENSP00000390644.2	Q8TC20-4

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000448

AC:

AN:

245344

Hom.:

AF XY:

0.0000451

AC XY:

AN XY:

132932

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:

0.0000991

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1455768

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

724196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.000157

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.000112

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0015

.;.;.;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.36

T;T;T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.018

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.3

.;.;.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

1.8

N;N;N;N;N

REVEL

Benign

0.0060

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;.;B;B

Vest4

0.19

MVP

0.099

MPC

0.11

ClinPred

0.025

GERP RS

1.5

Varity_R

0.029

gMVP

0.016

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.

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