Variant rs9288952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181780.4(BTLA):c.800C>T(p.Pro267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 1,612,738 control chromosomes in the GnomAD database, including 674,193 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.74 ( 48080 hom., cov: 32)

Exomes 𝑓: 0.92 ( 626113 hom. )

Consequence

BTLA
NM_181780.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

BTLA (HGNC:21087): (B and T lymphocyte associated) This gene encodes a member of the immunoglobulin superfamily. The encoded protein contains a single immunoglobulin (Ig) domain and is a receptor that relays inhibitory signals to suppress the immune response. Alternative splicing results in multiple transcript variants. Polymorphisms in this gene have been associated with an increased risk of rheumatoid arthritis. [provided by RefSeq, Aug 2011]

BTLA links:

BTLA (HGNC:):

BTLA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.8478456E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTLA	NM_181780.4 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	5/5	ENST00000334529.10	NP_861445.4	Q7Z6A9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BTLA	ENST00000334529.10 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	5/5	1	NM_181780.4	ENSP00000333919.5	Q7Z6A9-1
BTLA	ENST00000383680.4 linkuse as main transcript	c.656C>T	p.Pro219Leu	missense_variant	4/4	1		ENSP00000373178.4	Q7Z6A9-2
BTLA	ENST00000474965.1 linkuse as main transcript	n.304C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112243

AN:

151996

Hom.:

48076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.928

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.958

Gnomad OTH

AF:

0.782

GnomAD3 exomes

AF:

0.836

AC:

209705

AN:

250910

Hom.:

92224

AF XY:

0.855

AC XY:

115882

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.928

Gnomad EAS exome

AF:

0.722

Gnomad SAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.967

Gnomad NFE exome

AF:

0.956

Gnomad OTH exome

AF:

0.882

GnomAD4 exome

AF:

0.917

AC:

1339490

AN:

1460624

Hom.:

626113

Cov.:

AF XY:

0.917

AC XY:

666434

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.673

Gnomad4 ASJ exome

AF:

0.929

Gnomad4 EAS exome

AF:

0.728

Gnomad4 SAS exome

AF:

0.826

Gnomad4 FIN exome

AF:

0.967

Gnomad4 NFE exome

AF:

0.961

Gnomad4 OTH exome

AF:

0.878

GnomAD4 genome

AF:

0.738

AC:

112249

AN:

152114

Hom.:

48080

Cov.:

AF XY:

0.741

AC XY:

55164

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.928

Gnomad4 EAS

AF:

0.726

Gnomad4 SAS

AF:

0.816

Gnomad4 FIN

AF:

0.971

Gnomad4 NFE

AF:

0.958

Gnomad4 OTH

AF:

0.783

Alfa

AF:

0.905

Hom.:

158140

Bravo

AF:

0.698

TwinsUK

AF:

0.965

AC:

3577

ALSPAC

AF:

0.971

AC:

3743

ESP6500AA

AF:

0.296

AC:

1302

ESP6500EA

AF:

0.958

AC:

8240

ExAC

AF:

0.833

AC:

101127

Asia WGS

AF:

0.756

AC:

2630

AN:

3478

EpiCase

AF:

0.954

EpiControl

AF:

0.951

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.4

DANN

Benign

0.25

DEOGEN2

Benign

0.083

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

7.8e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.0090

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.010

MPC

0.63

ClinPred

0.0000096

GERP RS

-0.71

Varity_R

0.019

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over