Genetic Variant CT47B1:p.Glu266Lys (chrX-120874000-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001145718.3(CT47B1):c.796G>A(p.Glu266Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., 2 hem., cov: 12)

Exomes 𝑓: 0.0018 ( 5 hom. 221 hem. )

Failed GnomAD Quality Control

Consequence

CT47B1
NM_001145718.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036537647).

BP6

Variant X-120874000-C-T is Benign according to our data. Variant chrX-120874000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661333.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00182 (717/393148) while in subpopulation EAS AF= 0.0223 (526/23544). AF 95% confidence interval is 0.0208. There are 5 homozygotes in gnomad4_exome. There are 221 alleles in male gnomad4_exome subpopulation. Median coverage is 6. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CT47B1	NM_001145718.3 link	c.796G>A	p.Glu266Lys	missense_variant	Exon 2 of 3	ENST00000371311.5	NP_001139190.1	P0C2W7
CT47B1	XM_017029734.3 link	c.793G>A	p.Glu265Lys	missense_variant	Exon 2 of 3		XP_016885223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CT47B1	ENST00000371311.5 link	c.796G>A	p.Glu266Lys	missense_variant	Exon 2 of 3	5	NM_001145718.3	ENSP00000360360.3		P0C2W7

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

80322

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

12454

show subpopulations

Gnomad AFR

AF:

0.0000501

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000155

Gnomad ASJ

AF:

0.00366

Gnomad EAS

AF:

0.00831

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000185

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00201

AC:

104

AN:

51671

Hom.:

AF XY:

0.00201

AC XY:

AN XY:

15937

show subpopulations

Gnomad AFR exome

AF:

0.000401

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.00927

Gnomad SAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.000558

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00182

AC:

717

AN:

393148

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

221

AN XY:

123970

show subpopulations

Gnomad4 AFR exome

AF:

0.0000925

Gnomad4 AMR exome

AF:

0.0000683

Gnomad4 ASJ exome

AF:

0.00636

Gnomad4 EAS exome

AF:

0.0223

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.0000431

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.000956

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000461

AC:

AN:

80332

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

12480

show subpopulations

Gnomad4 AFR

AF:

0.0000501

Gnomad4 AMR

AF:

0.000154

Gnomad4 ASJ

AF:

0.00366

Gnomad4 EAS

AF:

0.00834

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000185

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000914

Hom.:

Bravo

AF:

0.000567

ExAC

AF:

0.00148

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CT47B1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.072

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.042

Polyphen

1.0

Vest4

0.037

MutPred

0.21

Gain of methylation at E266 (P = 0.0114);

MVP

0.048

MPC

0.0052

ClinPred

0.027

GERP RS

1.8

Varity_R

0.39

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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