rs35037492

Positions:

• chr6-32396063-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001304561.2(BTNL2):​c.1054G>A​(p.Ala352Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 1,612,728 control chromosomes in the GnomAD database, including 12 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 0.0053 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (4 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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]

BTNL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002585739).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00529 (806/152290) while in subpopulation AFR AF= 0.0183 (761/41560). AF 95% confidence interval is 0.0172. There are 8 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.1054G>A	p.Ala352Thr	missense_variant	5/8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-9391C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.1054G>A	p.Ala352Thr	missense_variant	5/8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.00526 AC: 801 AN: 152172 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00145 AC: 357 AN: 245826 Hom.: 3 AF XY: 0.00100 AC XY: 134 AN XY: 133918

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000636

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000531 AC: 776 AN: 1460438 Hom.: 4 Cov.: 35 AF XY: 0.000461 AC XY: 335 AN XY: 726502

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00529 AC: 806 AN: 152290 Hom.: 8 Cov.: 33 AF XY: 0.00490 AC XY: 365 AN XY: 74448

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00108 Hom.: 2

Bravo AF: 0.00605

ESP6500AA AF: 0.0179 AC: 54

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00174 AC: 205

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.48	N
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	.;N;D
REVEL	Benign	0.028
Sift	Benign	0.096	.;T;D
Sift4G	Benign	0.22	T;T;T
Polyphen		0.25	.;B;.
Vest4		0.070
MVP		0.15
MPC		0.77
ClinPred		0.018	T
GERP RS		1.3
Varity_R		0.084
gMVP		0.34

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: rs35037492; hg19: chr6-32363840;