rs28362678

chr6-32394968-G-Achr6-32394968-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):c.1136C>T(p.Pro379Leu) variant causes a missense change. The variant allele was found at a frequency of 0.153 in 1,610,580 control chromosomes in the GnomAD database, including 20,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 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 0.15 (1814 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18318 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014532506).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.1136C>T	p.Pro379Leu	missense_variant	6/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-10486G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.1136C>T	p.Pro379Leu	missense_variant	6/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.627+4215G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22977 AN: 151924 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.153 AC: 38173 AN: 249352 Hom.: 3243 AF XY: 0.154 AC XY: 20761 AN XY: 134770

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0787

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.153 AC: 223713 AN: 1458538 Hom.: 18318 Cov.: 33 AF XY: 0.154 AC XY: 111459 AN XY: 725386

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0807

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.151 AC: 22977 AN: 152042 Hom.: 1814 Cov.: 32 AF XY: 0.157 AC XY: 11642 AN XY: 74314

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0791

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.151

Alfa AF: 0.141 Hom.: 2293

Bravo AF: 0.137

TwinsUK AF: 0.122 AC: 451

ALSPAC AF: 0.129 AC: 498

ESP6500AA AF: 0.125 AC: 551

ESP6500EA AF: 0.144 AC: 1241

ExAC AF: 0.155 AC: 18765

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	3.8
Dann	Benign	0.73
DEOGEN2	Benign	0.0028	T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00036	N
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.44	T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.085
MPC		0.37
ClinPred		0.0066	T
GERP RS		2.6
Varity_R		0.043
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs28362678; hg19: chr6-32362745; COSMIC: COSV66630186; COSMIC: COSV66630186;