Genetic Variant NM_001170692.2:c.1696G>A (chr6-7373123-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001170692.2(CAGE1):c.1696G>A(p.Ala566Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

Publications

0 publications found

Variant links:

Genes affected

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

CAGE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020914942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170692.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAGE1	NM_001170692.2	MANE Select	c.1696G>A	p.Ala566Thr	missense	Exon 5 of 14	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2		c.1696G>A	p.Ala566Thr	missense	Exon 5 of 13	NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3		c.1288G>A	p.Ala430Thr	missense	Exon 4 of 11	NP_995586.1	Q8TC20-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAGE1	ENST00000502583.6	TSL:5 MANE Select	c.1696G>A	p.Ala566Thr	missense	Exon 5 of 14	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000338150.8	TSL:2	c.1696G>A	p.Ala566Thr	missense	Exon 5 of 13	ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000379918.8	TSL:5	c.1696G>A	p.Ala566Thr	missense	Exon 5 of 14	ENSP00000369250.4	E7EUJ7

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000686

AC:

AN:

247910

AF XY:

0.0000372

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.0000293

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:

0.0000212

AC:

AN:

1460494

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726456

show subpopulations

African (AFR)

AF:

0.000809

AC:

AN:

33392

American (AMR)

AF:

0.0000450

AC:

AN:

44444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111454

Other (OTH)

AF:

0.0000331

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000322

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41580

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.00135

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000745

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.59

M_CAP

Benign

0.0057

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.36

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

REVEL

Benign

0.073

Sift

Benign

0.28

Sift4G

Benign

0.49

Polyphen

0.13

Vest4

0.092

MVP

0.36

MPC

0.084

ClinPred

0.021

GERP RS

2.9

Varity_R

0.036

gMVP

0.049

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over