Genetic Variant NM_001304561.2:c.1140G>A (chr6-32394964-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.1140G>A(p.Met380Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,610,748 control chromosomes in the GnomAD database, including 20,129 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 0.15 ( 1810 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18319 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

Publications

32 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=0.026081413).

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.1140G>A	p.Met380Ile	missense_variant	Exon 6 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-10490C>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.1140G>A	p.Met380Ile	missense_variant	Exon 6 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22975

AN:

151978

Hom.:

1810

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

GnomAD2 exomes

AF:

0.153

AC:

38301

AN:

249680

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0789

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.153

AC:

223731

AN:

1458652

Hom.:

18319

Cov.:

AF XY:

0.154

AC XY:

111479

AN XY:

725472

show subpopulations

African (AFR)

AF:

0.133

AC:

4438

AN:

33424

American (AMR)

AF:

0.145

AC:

6473

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.0806

AC:

2099

AN:

26036

East Asian (EAS)

AF:

0.235

AC:

9301

AN:

39528

South Asian (SAS)

AF:

0.170

AC:

14608

AN:

85772

European-Finnish (FIN)

AF:

0.261

AC:

13933

AN:

53314

Middle Eastern (MID)

AF:

0.105

AC:

605

AN:

5758

European-Non Finnish (NFE)

AF:

0.148

AC:

163820

AN:

1110010

Other (OTH)

AF:

0.140

AC:

8454

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

10392

20784

31175

41567

51959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5902

11804

17706

23608

29510

<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:

0.151

AC:

22975

AN:

152096

Hom.:

1810

Cov.:

AF XY:

0.157

AC XY:

11643

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.133

AC:

5526

AN:

41524

American (AMR)

AF:

0.138

AC:

2109

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0791

AC:

274

AN:

3466

East Asian (EAS)

AF:

0.151

AC:

781

AN:

5164

South Asian (SAS)

AF:

0.184

AC:

884

AN:

4800

European-Finnish (FIN)

AF:

0.269

AC:

2844

AN:

10556

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9988

AN:

67988

Other (OTH)

AF:

0.151

AC:

319

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

957

1914

2870

3827

4784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.142

Hom.:

3565

Bravo

AF:

0.137

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.128

AC:

494

ESP6500AA

AF:

0.125

AC:

551

ESP6500EA

AF:

0.144

AC:

1241

ExAC

AF:

0.154

AC:

18762

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

0.15

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.5

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0020

T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.047

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;.

PhyloP100

0.0050

PrimateAI

Benign

0.35

PROVEAN

Benign

0.14

.;N;N

REVEL

Benign

0.095

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.047

MutPred

0.13

Loss of disorder (P = 0.0591);Loss of disorder (P = 0.0591);.;

MPC

0.40

ClinPred

0.0096

GERP RS

3.3

Varity_R

0.27

gMVP

0.28

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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