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rs2076530

Variant summary

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

The NM_001304561.2(BTNL2):c.1078A>G(p.Ser360Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,605,698 control chromosomes in the GnomAD database, including 154,229 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.40 ( 12372 hom., cov: 32)
Exomes 𝑓: 0.44 ( 141857 hom. )

Consequence

BTNL2
NM_001304561.2 missense, splice_region

Scores

13
Splicing: ADA: 0.00002158
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72
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]
TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

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=0.0020704567).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BTNL2NM_001304561.2 linkuse as main transcriptc.1078A>G p.Ser360Gly missense_variant, splice_region_variant 5/8 ENST00000454136.8
TSBP1-AS1NR_136245.1 linkuse as main transcriptn.303-9415T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BTNL2ENST00000454136.8 linkuse as main transcriptc.1078A>G p.Ser360Gly missense_variant, splice_region_variant 5/85 NM_001304561.2 P1
TSBP1-AS1ENST00000645134.1 linkuse as main transcriptn.627+5286T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.402
AC:
61050
AN:
152002
Hom.:
12370
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.333
Gnomad AMI
AF:
0.474
Gnomad AMR
AF:
0.442
Gnomad ASJ
AF:
0.411
Gnomad EAS
AF:
0.315
Gnomad SAS
AF:
0.431
Gnomad FIN
AF:
0.457
Gnomad MID
AF:
0.363
Gnomad NFE
AF:
0.429
Gnomad OTH
AF:
0.400
GnomAD3 exomes
AF:
0.423
AC:
103271
AN:
244188
Hom.:
22391
AF XY:
0.422
AC XY:
56164
AN XY:
133068
show subpopulations
Gnomad AFR exome
AF:
0.330
Gnomad AMR exome
AF:
0.497
Gnomad ASJ exome
AF:
0.405
Gnomad EAS exome
AF:
0.318
Gnomad SAS exome
AF:
0.399
Gnomad FIN exome
AF:
0.460
Gnomad NFE exome
AF:
0.430
Gnomad OTH exome
AF:
0.433
GnomAD4 exome
AF:
0.439
AC:
638248
AN:
1453578
Hom.:
141857
Cov.:
32
AF XY:
0.437
AC XY:
315523
AN XY:
722736
show subpopulations
Gnomad4 AFR exome
AF:
0.319
Gnomad4 AMR exome
AF:
0.493
Gnomad4 ASJ exome
AF:
0.408
Gnomad4 EAS exome
AF:
0.408
Gnomad4 SAS exome
AF:
0.402
Gnomad4 FIN exome
AF:
0.457
Gnomad4 NFE exome
AF:
0.446
Gnomad4 OTH exome
AF:
0.416
GnomAD4 genome
AF:
0.401
AC:
61070
AN:
152120
Hom.:
12372
Cov.:
32
AF XY:
0.403
AC XY:
29967
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.333
Gnomad4 AMR
AF:
0.442
Gnomad4 ASJ
AF:
0.411
Gnomad4 EAS
AF:
0.315
Gnomad4 SAS
AF:
0.431
Gnomad4 FIN
AF:
0.457
Gnomad4 NFE
AF:
0.429
Gnomad4 OTH
AF:
0.394
Alfa
AF:
0.416
Hom.:
22359
Bravo
AF:
0.402
TwinsUK
AF:
0.447
AC:
1657
ALSPAC
AF:
0.471
AC:
1814
ESP6500AA
AF:
0.323
AC:
974
ESP6500EA
AF:
0.438
AC:
2375
ExAC
AF:
0.418
AC:
48947
Asia WGS
AF:
0.330
AC:
1149
AN:
3478
EpiCase
AF:
0.420
EpiControl
AF:
0.420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.051
BayesDel_addAF
Benign
-0.79
T
BayesDel_noAF
Benign
-0.77
Cadd
Benign
15
Dann
Benign
0.60
DEOGEN2
Benign
0.0029
T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.0046
N
MetaRNN
Benign
0.0021
T;T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
0.99
P;P;P;P;P;P;P
PrimateAI
Benign
0.37
T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.039
MPC
0.33
ClinPred
0.0014
T
GERP RS
3.4
Varity_R
0.053
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000022
dbscSNV1_RF
Benign
0.044
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2076530; hg19: chr6-32363816; COSMIC: COSV66630224; COSMIC: COSV66630224; API