dbSNP rs28362678: BTNL2:p.Pro379Leu (chr6-32394968-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304561.2(BTNL2):c.1136C>T(p.Pro379Leu) variant causes a missense change. The variant allele was found at a frequency of 0.153 in 1,610,580 control chromosomes in the GnomAD database, including 20,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1814 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18318 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014532506).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1136C>T	p.Pro379Leu	missense_variant	Exon 6 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-10486G>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.1136C>T	p.Pro379Leu	missense_variant	Exon 6 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22977

AN:

151924

Hom.:

1814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0791

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.153

AC:

38173

AN:

249352

Hom.:

3243

AF XY:

0.154

AC XY:

20761

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.0787

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.153

AC:

223713

AN:

1458538

Hom.:

18318

Cov.:

AF XY:

0.154

AC XY:

111459

AN XY:

725386

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0807

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.151

AC:

22977

AN:

152042

Hom.:

1814

Cov.:

AF XY:

0.157

AC XY:

11642

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0791

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.141

Hom.:

2293

Bravo

AF:

0.137

TwinsUK

AF:

0.122

AC:

451

ALSPAC

AF:

0.129

AC:

498

ESP6500AA

AF:

0.125

AC:

551

ESP6500EA

AF:

0.144

AC:

1241

ExAC

AF:

0.155

AC:

18765

Asia WGS

AF:

0.155

AC:

538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.8

DANN

Benign

0.73

DEOGEN2

Benign

0.0028

T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00036

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-3.8

.;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

1.4

.;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.085

MPC

0.37

ClinPred

0.0066

GERP RS

2.6

Varity_R

0.043

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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