Genetic Variant BTNL2:c.79+227T>C (chr6-32406818-A-G) – 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.79+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 395,194 control chromosomes in the GnomAD database, including 3,564 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 ( 1270 hom., cov: 32)

Exomes 𝑓: 0.12 ( 2294 hom. )

Consequence

BTNL2
NM_001304561.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.775

Publications

13 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.79+227T>C		intron_variant	Intron 1 of 7	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.1108A>G		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.79+227T>C		intron_variant	Intron 1 of 7	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18714

AN:

152042

Hom.:

1271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.120

AC:

29153

AN:

243034

Hom.:

2294

Cov.:

AF XY:

0.118

AC XY:

14692

AN XY:

124672

show subpopulations

African (AFR)

AF:

0.116

AC:

1061

AN:

9186

American (AMR)

AF:

0.0705

AC:

853

AN:

12092

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

800

AN:

8376

East Asian (EAS)

AF:

0.0335

AC:

716

AN:

21388

South Asian (SAS)

AF:

0.0159

AC:

213

AN:

13376

European-Finnish (FIN)

AF:

0.139

AC:

2082

AN:

14972

Middle Eastern (MID)

AF:

0.0498

AC:

AN:

1164

European-Non Finnish (NFE)

AF:

0.147

AC:

21573

AN:

146986

Other (OTH)

AF:

0.116

AC:

1797

AN:

15494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1206

2412

3619

4825

6031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.123

AC:

18720

AN:

152160

Hom.:

1270

Cov.:

AF XY:

0.117

AC XY:

8681

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.114

AC:

4723

AN:

41514

American (AMR)

AF:

0.0732

AC:

1119

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

332

AN:

3468

East Asian (EAS)

AF:

0.0336

AC:

174

AN:

5174

South Asian (SAS)

AF:

0.0197

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.141

AC:

1489

AN:

10590

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10448

AN:

67968

Other (OTH)

AF:

0.104

AC:

219

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

801

1603

2404

3206

4007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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.:

3435

Bravo

AF:

0.118

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.81

PhyloP100

-0.78

PromoterAI

-0.0093

Neutral

(source)

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