rs41417449

chr6-32396234-T-C

Variant summary

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

The NM_001304561.2(BTNL2):c.883A>G(p.Met295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,612,956 control chromosomes in the GnomAD database, including 1,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.012 (68 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1057 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=0.0016432703).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.883A>G	p.Met295Val	missense_variant	5/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-9220T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.883A>G	p.Met295Val	missense_variant	5/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.627+5481T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1859 AN: 152142 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0232 AC: 5722 AN: 246684 Hom.: 182 AF XY: 0.0262 AC XY: 3527 AN XY: 134410

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.00946

Gnomad ASJ exome AF: 0.0498

Gnomad EAS exome AF: 0.0823

Gnomad SAS exome AF: 0.0817

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00684

Gnomad OTH exome AF: 0.0218

GnomAD4 exome AF: 0.0154 AC: 22510 AN: 1460696 Hom.: 1057 Cov.: 33 AF XY: 0.0179 AC XY: 12974 AN XY: 726682

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00993

Gnomad4 ASJ exome AF: 0.0489

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0828

Gnomad4 FIN exome AF: 0.000267

Gnomad4 NFE exome AF: 0.00521

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0122 AC: 1857 AN: 152260 Hom.: 68 Cov.: 32 AF XY: 0.0142 AC XY: 1054 AN XY: 74454

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.0453

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0102 Hom.: 23

Bravo AF: 0.00989

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00132 AC: 4

ESP6500EA AF: 0.00886 AC: 48

ExAC AF: 0.0237 AC: 2815

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.069
Dann	Benign	0.47
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.022
MPC		0.37
ClinPred		0.011	T
GERP RS		-10
Varity_R		0.10
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41417449; hg19: chr6-32364011; COSMIC: COSV66630201; COSMIC: COSV66630201;