Genetic Variant BTNL2:p.Asp336Asn (chr6-32396111-C-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.1006G>A(p.Asp336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,088 control chromosomes in the GnomAD database, including 1,128 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.

Frequency

Genomes: 𝑓 0.012 ( 68 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1060 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

22 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=0.004987538).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1006G>A	p.Asp336Asn	missense_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1 link	n.303-9343C>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.1006G>A	p.Asp336Asn	missense_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1861

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0232

AC:

5725

AN:

246562

AF XY:

0.0263

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00946

Gnomad ASJ exome

AF:

0.0498

Gnomad EAS exome

AF:

0.0824

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00685

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0155

AC:

22571

AN:

1460774

Hom.:

1060

Cov.:

AF XY:

0.0179

AC XY:

12998

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33480

American (AMR)

AF:

0.00993

AC:

444

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1279

AN:

26136

East Asian (EAS)

AF:

0.162

AC:

6415

AN:

39700

South Asian (SAS)

AF:

0.0828

AC:

7145

AN:

86248

European-Finnish (FIN)

AF:

0.000268

AC:

AN:

52326

Middle Eastern (MID)

AF:

0.0383

AC:

221

AN:

5766

European-Non Finnish (NFE)

AF:

0.00524

AC:

5828

AN:

1112008

Other (OTH)

AF:

0.0195

AC:

1176

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1200

2399

3599

4798

5998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0122

AC:

1859

AN:

152314

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41562

American (AMR)

AF:

0.00928

AC:

142

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

566

AN:

5178

South Asian (SAS)

AF:

0.100

AC:

483

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00551

AC:

375

AN:

68036

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00990

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00132

AC:

ESP6500EA

AF:

0.00904

AC:

ExAC

AF:

0.0237

AC:

2811

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0064

T;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.054

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.24

.;N;.

PhyloP100

-0.11

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.91

.;N;N

REVEL

Benign

0.016

Sift

Benign

0.90

.;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.092

.;B;.

Vest4

0.020

MPC

0.41

ClinPred

0.0072

GERP RS

2.3

Varity_R

0.094

gMVP

0.32

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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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