6-32405086-A-T

Variant names:

• chr6-32405086-A-T
• rs28362682
• NM_001304561.2:c.280T>A

Variant summary

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

The NM_001304561.2(BTNL2):​c.280T>A​(p.Trp94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,612,784 control chromosomes in the GnomAD database, including 7,048 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 0.10 (967 hom., cov: 32)
  • Exomes 𝑓: 0.080 (6081 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 21 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=0.0035823584).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 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.280T>A	p.Trp94Arg	missense	Exon 2 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-368A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.280T>A	p.Trp94Arg	missense	Exon 2 of 8	ENSP00000390613.3
	BTNL2	ENST00000446536.3	TSL:1	c.277T>A	p.Trp93Arg	missense	Exon 2 of 2	ENSP00000388434.2
	BTNL2	ENST00000465865.6	TSL:1	n.191+89T>A		intron	N/A	ENSP00000420063.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15859 AN: 151890 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.115 AC: 28409 AN: 247066 AF XY: 0.109

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.0353

Gnomad EAS exome AF: 0.203

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.0766

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0798 AC: 116519 AN: 1460776 Hom.: 6081 Cov.: 31 AF XY: 0.0797 AC XY: 57891 AN XY: 726704

African (AFR) AF: 0.123 AC: 4129 AN: 33480

American (AMR) AF: 0.192 AC: 8594 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0356 AC: 931 AN: 26136

East Asian (EAS) AF: 0.190 AC: 7534 AN: 39700

South Asian (SAS) AF: 0.0856 AC: 7385 AN: 86258

European-Finnish (FIN) AF: 0.169 AC: 8866 AN: 52320

Middle Eastern (MID) AF: 0.0595 AC: 343 AN: 5768

European-Non Finnish (NFE) AF: 0.0661 AC: 73482 AN: 1112004

Other (OTH) AF: 0.0870 AC: 5255 AN: 60386

GnomAD4 genome AF: 0.104 AC: 15869 AN: 152008 Hom.: 967 Cov.: 32 AF XY: 0.109 AC XY: 8104 AN XY: 74294

African (AFR) AF: 0.119 AC: 4942 AN: 41468

American (AMR) AF: 0.132 AC: 2023 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5160

South Asian (SAS) AF: 0.0919 AC: 442 AN: 4812

European-Finnish (FIN) AF: 0.178 AC: 1870 AN: 10534

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5160 AN: 67980

Other (OTH) AF: 0.115 AC: 242 AN: 2108

Alfa AF: 0.0772 Hom.: 418

Bravo AF: 0.102

TwinsUK AF: 0.0583 AC: 216

ALSPAC AF: 0.0656 AC: 253

ESP6500AA AF: 0.113 AC: 340

ESP6500EA AF: 0.0790 AC: 428

ExAC AF: 0.112 AC: 13279

Asia WGS AF: 0.139 AC: 484 AN: 3478

EpiCase AF: 0.0701

EpiControl AF: 0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.035
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.4
DANN	Benign	0.27
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.8	N
PhyloP100		0.24
PrimateAI	Benign	0.37	T
PROVEAN	Benign	5.7	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.33		Gain of disorder (P = 0.0181)
MPC		0.64
ClinPred		0.00079	T
GERP RS		3.0
Varity_R		0.083
gMVP		0.33
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: rs28362682; hg19: chr6-32372863; COSMIC: COSV66630140;