rs2076530

Variant names:

• chr6-32396039-T-C
• rs2076530
• NM_001304561.2:c.1078A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12372 hom., cov: 32)
  • Exomes 𝑓: 0.44 (141857 hom.)
• Consequence: BTNL2 NM_001304561.2 missense, splice_region
• Scores: Splicing: ADA: 0.00002158
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 149 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.1078A>G	p.Ser360Gly	missense splice_region	Exon 5 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-9415T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.1078A>G	p.Ser360Gly	missense splice_region	Exon 5 of 8	ENSP00000390613.3
	BTNL2	ENST00000544175.3	TSL:1	n.*339A>G		splice_region non_coding_transcript_exon	Exon 4 of 5	ENSP00000443364.2
	BTNL2	ENST00000544175.3	TSL:1	n.*339A>G		3_prime_UTR	Exon 4 of 5	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61050 AN: 152002 Hom.: 12370 Cov.: 32

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

GnomAD2 exomes AF: 0.423 AC: 103271 AN: 244188 AF XY: 0.422

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 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

African (AFR) AF: 0.319 AC: 10649 AN: 33362

American (AMR) AF: 0.493 AC: 21957 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 10571 AN: 25924

East Asian (EAS) AF: 0.408 AC: 16144 AN: 39604

South Asian (SAS) AF: 0.402 AC: 34524 AN: 85866

European-Finnish (FIN) AF: 0.457 AC: 23819 AN: 52168

Middle Eastern (MID) AF: 0.364 AC: 2091 AN: 5752

European-Non Finnish (NFE) AF: 0.446 AC: 493490 AN: 1106236

Other (OTH) AF: 0.416 AC: 25003 AN: 60104

GnomAD4 genome AF: 0.401 AC: 61070 AN: 152120 Hom.: 12372 Cov.: 32 AF XY: 0.403 AC XY: 29967 AN XY: 74350

African (AFR) AF: 0.333 AC: 13806 AN: 41506

American (AMR) AF: 0.442 AC: 6749 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1632 AN: 5174

South Asian (SAS) AF: 0.431 AC: 2081 AN: 4826

European-Finnish (FIN) AF: 0.457 AC: 4833 AN: 10568

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29176 AN: 67988

Other (OTH) AF: 0.394 AC: 832 AN: 2112

Alfa AF: 0.416 Hom.: 34029

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 v4.9

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
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0046	N
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N
PhyloP100		1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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
Mutation Taster		=77/23	polymorphism (auto)

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

Other links and lift over

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