dbSNP rs28362675: BTNL2:p.Glu454* (chr6-32394744-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001304561.2(BTNL2):c.1360G>T(p.Glu454*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,610,994 control chromosomes in the GnomAD database, including 1,121 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. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.012 ( 67 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1054 hom. )

Consequence

BTNL2
NM_001304561.2 stop_gained, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

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 -8 ACMG points.

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.1360G>T	p.Glu454*	stop_gained, splice_region_variant	Exon 6 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-10710C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.1360G>T	p.Glu454*	stop_gained, splice_region_variant	Exon 6 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1861

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

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:

0.0228

AC:

5712

AN:

250106

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00936

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0821

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0154

AC:

22420

AN:

1458668

Hom.:

1054

Cov.:

AF XY:

0.0178

AC XY:

12895

AN XY:

725040

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

33432

American (AMR)

AF:

0.00990

AC:

442

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1269

AN:

26054

East Asian (EAS)

AF:

0.161

AC:

6393

AN:

39598

South Asian (SAS)

AF:

0.0824

AC:

7081

AN:

85920

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.0382

AC:

220

AN:

5756

European-Non Finnish (NFE)

AF:

0.00522

AC:

5787

AN:

1109636

Other (OTH)

AF:

0.0193

AC:

1165

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

991

1982

2973

3964

4955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0122

AC:

1859

AN:

152326

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41572

American (AMR)

AF:

0.00921

AC:

141

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

567

AN:

5178

South Asian (SAS)

AF:

0.100

AC:

483

AN:

4828

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:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

169

253

338

422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.0235

AC:

2858

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.83

PhyloP100

1.8

Vest4

0.28

ClinPred

0.068

GERP RS

2.1

Varity_R

0.12

Mutation Taster

=186/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.38

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs28362675

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