Variant 3-112471290-G-T 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.469C>A(p.Arg157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,614,114 control chromosomes in the GnomAD database, including 804,165 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 0.99 ( 74813 hom., cov: 31)

Exomes 𝑓: 1.0 ( 729352 hom. )

Consequence

BTLA
NM_181780.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

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=7.1498323E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.469C>A	p.Arg157Ser	missense_variant	3/5	ENST00000334529.10	NP_861445.4	Q7Z6A9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10 linkuse as main transcript	c.469C>A	p.Arg157Ser	missense_variant	3/5	1	NM_181780.4	ENSP00000333919.5		Q7Z6A9-1
BTLA	ENST00000383680.4 linkuse as main transcript	c.404-1486C>A		intron_variant		1		ENSP00000373178.4		Q7Z6A9-2

Frequencies

GnomAD3 genomes

AF:

0.991

AC:

150825

AN:

152164

Hom.:

74759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.997

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.992

GnomAD3 exomes

AF:

0.997

AC:

250749

AN:

251438

Hom.:

125040

AF XY:

0.998

AC XY:

135624

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.994

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1460239

AN:

1461832

Hom.:

729352

Cov.:

AF XY:

0.999

AC XY:

726514

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.967

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.995

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.991

AC:

150938

AN:

152282

Hom.:

74813

Cov.:

AF XY:

0.992

AC XY:

73851

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.970

Gnomad4 AMR

AF:

0.997

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.992

Alfa

AF:

0.998

Hom.:

144848

Bravo

AF:

0.990

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.972

AC:

4284

ESP6500EA

AF:

1.00

AC:

8600

ExAC

AF:

0.997

AC:

121035

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.14

DANN

Benign

0.38

DEOGEN2

Benign

0.093

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.068

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.22

PROVEAN

Benign

1.3

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.045

MPC

0.69

ClinPred

0.010

GERP RS

-4.9

Varity_R

0.10

gMVP

0.34

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