dbSNP rs76844316: BTLA:p.Asn197Thr (chr3-112469762-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_181780.4(BTLA):c.590A>C(p.Asn197Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,600,692 control chromosomes in the GnomAD database, including 520 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.023 ( 90 hom., cov: 31)

Exomes 𝑓: 0.0071 ( 430 hom. )

Consequence

BTLA
NM_181780.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

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:

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=0.0020754635).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4 link	c.590A>C	p.Asn197Thr	missense_variant	Exon 4 of 5	ENST00000334529.10	NP_861445.4	Q7Z6A9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTLA	ENST00000334529.10 link	c.590A>C	p.Asn197Thr	missense_variant	Exon 4 of 5	1	NM_181780.4	ENSP00000333919.5	Q7Z6A9-1
BTLA	ENST00000383680.4 link	c.446A>C	p.Asn149Thr	missense_variant	Exon 3 of 4	1		ENSP00000373178.4	Q7Z6A9-2
BTLA	ENST00000474965.1 link	n.94A>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
BTLA	ENST00000496584.1 link	n.525A>C		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3239

AN:

142018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0490

Gnomad AMI

AF:

0.00234

Gnomad AMR

AF:

0.0582

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.00971

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.0236

AC:

5906

AN:

249746

Hom.:

287

AF XY:

0.0190

AC XY:

2573

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0687

Gnomad SAS exome

AF:

0.00651

Gnomad FIN exome

AF:

0.000244

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00711

AC:

10374

AN:

1458552

Hom.:

430

Cov.:

AF XY:

0.00655

AC XY:

4754

AN XY:

725742

show subpopulations

Gnomad4 AFR exome

AF:

0.0514

Gnomad4 AMR exome

AF:

0.0952

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0770

Gnomad4 SAS exome

AF:

0.00682

Gnomad4 FIN exome

AF:

0.000270

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.00864

GnomAD4 genome

AF:

0.0229

AC:

3255

AN:

142140

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1630

AN XY:

69274

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.0585

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0750

Gnomad4 SAS

AF:

0.00972

Gnomad4 FIN

AF:

0.000104

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.0181

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.0288

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0454

AC:

200

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0211

AC:

2557

Asia WGS

AF:

0.0370

AC:

130

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Uncertain

0.50

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.081

Sift

Benign

0.22

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0030

B;B

Vest4

0.055

MPC

0.64

ClinPred

0.0076

GERP RS

-0.53

Varity_R

0.080

gMVP

0.29

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