Genetic Variant CT47B1:p.Val289Ala (chrX-120873930-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001145718.3(CT47B1):c.866T>C(p.Val289Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000097 ( 0 hom., 0 hem., cov: 12)

Exomes 𝑓: 0.00012 ( 1 hom. 41 hem. )

Failed GnomAD Quality Control

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78

Publications

0 publications found

Variant links:

Genes affected

CT47B1 (HGNC:33293): (cancer/testis antigen family 47 member B1)

CT47B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018267512).

BP6

Variant X-120873930-A-G is Benign according to our data. Variant chrX-120873930-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2368018.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145718.3. 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
	CT47B1	NM_001145718.3	MANE Select	c.866T>C	p.Val289Ala	missense	Exon 2 of 3	NP_001139190.1	P0C2W7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CT47B1	ENST00000371311.5	TSL:5 MANE Select	c.866T>C	p.Val289Ala	missense	Exon 2 of 3	ENSP00000360360.3	P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.0000969

AC:

AN:

82543

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000143

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:

0.0000921

Gnomad OTH

AF:

0.000943

GnomAD2 exomes

AF:

0.000469

AC:

AN:

172591

AF XY:

0.000452

show subpopulations

Gnomad AFR exome

AF:

0.000469

Gnomad AMR exome

AF:

0.000404

Gnomad ASJ exome

AF:

0.000548

Gnomad EAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.000238

Gnomad NFE exome

AF:

0.000325

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000124

AC:

134

AN:

1079184

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

354424

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000267

AC:

AN:

26236

American (AMR)

AF:

0.000285

AC:

AN:

35052

Ashkenazi Jewish (ASJ)

AF:

0.000633

AC:

AN:

18963

East Asian (EAS)

AF:

0.000568

AC:

AN:

29919

South Asian (SAS)

AF:

0.000222

AC:

AN:

53938

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

29180

Middle Eastern (MID)

AF:

0.000618

AC:

AN:

3238

European-Non Finnish (NFE)

AF:

0.0000765

AC:

AN:

837133

Other (OTH)

AF:

0.000154

AC:

AN:

45525

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.268

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000969

AC:

AN:

82552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

15188

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000990

AC:

AN:

20204

American (AMR)

AF:

0.000143

AC:

AN:

6994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2222

East Asian (EAS)

AF:

0.00

AC:

AN:

2708

South Asian (SAS)

AF:

0.00

AC:

AN:

1657

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

167

European-Non Finnish (NFE)

AF:

0.0000921

AC:

AN:

43440

Other (OTH)

AF:

0.000925

AC:

AN:

1081

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

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:

0.00260

Hom.:

ExAC

AF:

0.0000505

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.049

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0090

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.0032

FATHMM_MKL

Benign

0.00070

LIST_S2

Benign

0.19

M_CAP

Benign

0.0083

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

-1.8

PrimateAI

Benign

0.23

PROVEAN

Benign

1.3

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.048

MutPred

0.13

Loss of ubiquitination at K292 (P = 0.0863)

MVP

0.26

MPC

0.0051

ClinPred

0.0013

GERP RS

-2.3

Varity_R

0.023

gMVP

0.0013

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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