Genetic Variant NM_001304561.2:c.280T>A (chr6-32405086-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304561.2(BTNL2):c.280T>A(p.Trp94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,612,784 control chromosomes in the GnomAD database, including 7,048 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 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 0.10 ( 967 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6081 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

21 publications found

Variant links:

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

BTNL2 links:

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

TSBP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035823584).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.280T>A	p.Trp94Arg	missense_variant	Exon 2 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-368A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.280T>A	p.Trp94Arg	missense_variant	Exon 2 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15859

AN:

151890

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0760

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.115

AC:

28409

AN:

247066

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0798

AC:

116519

AN:

1460776

Hom.:

6081

Cov.:

AF XY:

0.0797

AC XY:

57891

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.123

AC:

4129

AN:

33480

American (AMR)

AF:

0.192

AC:

8594

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0356

AC:

931

AN:

26136

East Asian (EAS)

AF:

0.190

AC:

7534

AN:

39700

South Asian (SAS)

AF:

0.0856

AC:

7385

AN:

86258

European-Finnish (FIN)

AF:

0.169

AC:

8866

AN:

52320

Middle Eastern (MID)

AF:

0.0595

AC:

343

AN:

5768

European-Non Finnish (NFE)

AF:

0.0661

AC:

73482

AN:

1112004

Other (OTH)

AF:

0.0870

AC:

5255

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7331

14663

21994

29326

36657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.104

AC:

15869

AN:

152008

Hom.:

967

Cov.:

AF XY:

0.109

AC XY:

8104

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.119

AC:

4942

AN:

41468

American (AMR)

AF:

0.132

AC:

2023

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3468

East Asian (EAS)

AF:

0.197

AC:

1019

AN:

5160

South Asian (SAS)

AF:

0.0919

AC:

442

AN:

4812

European-Finnish (FIN)

AF:

0.178

AC:

1870

AN:

10534

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0759

AC:

5160

AN:

67980

Other (OTH)

AF:

0.115

AC:

242

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

698

1397

2095

2794

3492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0772

Hom.:

418

Bravo

AF:

0.102

TwinsUK

AF:

0.0583

AC:

216

ALSPAC

AF:

0.0656

AC:

253

ESP6500AA

AF:

0.113

AC:

340

ESP6500EA

AF:

0.0790

AC:

428

ExAC

AF:

0.112

AC:

13279

Asia WGS

AF:

0.139

AC:

484

AN:

3478

EpiCase

AF:

0.0701

EpiControl

AF:

0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.4

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.0081

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.036

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-3.8

.;N;.

PhyloP100

0.24

PrimateAI

Benign

0.37

PROVEAN

Benign

5.7

.;N;N

REVEL

Benign

0.22

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

.;B;.

Vest4

0.064

MutPred

0.33

Gain of disorder (P = 0.0181);Gain of disorder (P = 0.0181);.;

MPC

0.64

ClinPred

0.00079

GERP RS

3.0

Varity_R

0.083

gMVP

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_001304561.2:c.280T>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over