NM_001304561.2:c.605C>T

Variant names:

• chr6-32403039-G-A
• rs28362680
• NM_001304561.2:c.605C>T

Variant summary

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

The NM_001304561.2(BTNL2):​c.605C>T​(p.Ala202Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,612,502 control chromosomes in the GnomAD database, including 11,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1345 hom., cov: 32)
  • Exomes 𝑓: 0.096 (9776 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=0.0053502023).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.605C>T	p.Ala202Val	missense_variant	Exon 3 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-2415G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.605C>T	p.Ala202Val	missense_variant	Exon 3 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18497 AN: 151930 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.139 AC: 34330 AN: 246410 Hom.: 3056 AF XY: 0.136 AC XY: 18281 AN XY: 134324

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0850

Gnomad EAS exome AF: 0.285

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.0832

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.0957 AC: 139714 AN: 1460454 Hom.: 9776 Cov.: 46 AF XY: 0.0979 AC XY: 71145 AN XY: 726540

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.0713

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.122 AC: 18510 AN: 152048 Hom.: 1345 Cov.: 32 AF XY: 0.128 AC XY: 9500 AN XY: 74332

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0942 Hom.: 1431

Bravo AF: 0.118

TwinsUK AF: 0.0623 AC: 231

ALSPAC AF: 0.0685 AC: 264

ESP6500AA AF: 0.132 AC: 398

ESP6500EA AF: 0.0879 AC: 476

ExAC AF: 0.137 AC: 16186

Asia WGS AF: 0.221 AC: 768 AN: 3478

EpiCase AF: 0.0781

EpiControl AF: 0.0758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.4
DANN	Benign	0.70
DEOGEN2	Benign	0.0022	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0055	N
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.1	.;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.0	.;N
REVEL	Benign	0.14
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.027
MPC		0.36
ClinPred		0.0049	T
GERP RS		4.4
Varity_R		0.029
gMVP		0.096

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

Publications

LitVar

Other links and lift over

dbSNP: rs28362680; hg19: chr6-32370816; COSMIC: COSV66631540; COSMIC: COSV66631540;