Genetic Variant BTNL2:c.80-249G>A (chr6-32405535-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.80-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 535,802 control chromosomes in the GnomAD database, including 5,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1361 hom., cov: 32)

Exomes 𝑓: 0.12 ( 4086 hom. )

Consequence

BTNL2
NM_001304561.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.47

Publications

65 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.80-249G>A		intron_variant	Intron 1 of 7	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.384C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.80-249G>A		intron_variant	Intron 1 of 7	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18558

AN:

152054

Hom.:

1358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.122

AC:

46660

AN:

383630

Hom.:

4086

Cov.:

AF XY:

0.123

AC XY:

25416

AN XY:

206256

show subpopulations

African (AFR)

AF:

0.132

AC:

1497

AN:

11302

American (AMR)

AF:

0.175

AC:

3730

AN:

21272

Ashkenazi Jewish (ASJ)

AF:

0.0849

AC:

1072

AN:

12622

East Asian (EAS)

AF:

0.354

AC:

7922

AN:

22386

South Asian (SAS)

AF:

0.166

AC:

7986

AN:

48152

European-Finnish (FIN)

AF:

0.168

AC:

3476

AN:

20638

Middle Eastern (MID)

AF:

0.114

AC:

193

AN:

1696

European-Non Finnish (NFE)

AF:

0.0817

AC:

18310

AN:

224030

Other (OTH)

AF:

0.115

AC:

2474

AN:

21532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1821

3641

5462

7282

9103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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:

0.122

AC:

18571

AN:

152172

Hom.:

1361

Cov.:

AF XY:

0.128

AC XY:

9548

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.140

AC:

5799

AN:

41496

American (AMR)

AF:

0.143

AC:

2191

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

273

AN:

3472

East Asian (EAS)

AF:

0.308

AC:

1597

AN:

5186

South Asian (SAS)

AF:

0.194

AC:

933

AN:

4820

European-Finnish (FIN)

AF:

0.178

AC:

1882

AN:

10580

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0816

AC:

5552

AN:

68002

Other (OTH)

AF:

0.134

AC:

282

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

803

1606

2408

3211

4014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0965

Hom.:

3721

Bravo

AF:

0.118

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.38

(source)

DANN

Benign

0.67

PhyloP100

-3.5

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