chr6-32403058-T-C

Variant names:

• chr6-32403058-T-C
• rs2076523
• NM_001304561.2:c.586A>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.586A>G​(p.Lys196Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,612,192 control chromosomes in the GnomAD database, including 113,868 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 0.36 (9938 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103930 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 62 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=8.492192E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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.586A>G	p.Lys196Glu	missense	Exon 3 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-2396T>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.586A>G	p.Lys196Glu	missense	Exon 3 of 8	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.192-1253A>G		intron	N/A	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.187-1253A>G		intron	N/A	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54679 AN: 151734 Hom.: 9934 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.397 AC: 97875 AN: 246372 AF XY: 0.392

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.554

Gnomad ASJ exome AF: 0.380

Gnomad EAS exome AF: 0.463

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.373 AC: 545112 AN: 1460340 Hom.: 103930 Cov.: 61 AF XY: 0.372 AC XY: 270478 AN XY: 726510

African (AFR) AF: 0.310 AC: 10376 AN: 33466

American (AMR) AF: 0.542 AC: 24242 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9954 AN: 26132

East Asian (EAS) AF: 0.483 AC: 19163 AN: 39690

South Asian (SAS) AF: 0.384 AC: 33134 AN: 86242

European-Finnish (FIN) AF: 0.364 AC: 19035 AN: 52300

Middle Eastern (MID) AF: 0.325 AC: 1876 AN: 5768

European-Non Finnish (NFE) AF: 0.364 AC: 404802 AN: 1111666

Other (OTH) AF: 0.373 AC: 22530 AN: 60366

GnomAD4 genome AF: 0.360 AC: 54705 AN: 151852 Hom.: 9938 Cov.: 31 AF XY: 0.362 AC XY: 26904 AN XY: 74222

African (AFR) AF: 0.319 AC: 13209 AN: 41390

American (AMR) AF: 0.438 AC: 6679 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3472

East Asian (EAS) AF: 0.453 AC: 2331 AN: 5142

South Asian (SAS) AF: 0.423 AC: 2029 AN: 4800

European-Finnish (FIN) AF: 0.362 AC: 3818 AN: 10542

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24200 AN: 67940

Other (OTH) AF: 0.365 AC: 770 AN: 2108

Alfa AF: 0.360 Hom.: 31854

Bravo AF: 0.371

TwinsUK AF: 0.373 AC: 1383

ALSPAC AF: 0.392 AC: 1511

ESP6500AA AF: 0.304 AC: 918

ESP6500EA AF: 0.370 AC: 2003

ExAC AF: 0.391 AC: 46003

Asia WGS AF: 0.385 AC: 1337 AN: 3478

EpiCase AF: 0.353

EpiControl AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.3
DANN	Benign	0.75
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0032	N
MetaRNN	Benign	0.000085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N
PhyloP100		-0.14
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.098
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.51
ClinPred		0.0014	T
GERP RS		2.6
Varity_R		0.048
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076523; hg19: chr6-32370835; COSMIC: COSV66630625; COSMIC: COSV66630625;