rs9268480

Positions:

• chr6-32396067-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304561.2(BTNL2):​c.1050G>A​(p.Gln350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,612,570 control chromosomes in the GnomAD database, including 62,843 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4552 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58291 hom.)
• Consequence: BTNL2 NM_001304561.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.035 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.1050G>A	p.Gln350=	synonymous_variant	5/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-9387C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.1050G>A	p.Gln350=	synonymous_variant	5/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.627+5314C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36297 AN: 152092 Hom.: 4553 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.258 AC: 63383 AN: 245970 Hom.: 8665 AF XY: 0.255 AC XY: 34227 AN XY: 134018

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.277 AC: 405220 AN: 1460360 Hom.: 58291 Cov.: 43 AF XY: 0.274 AC XY: 199227 AN XY: 726496

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.239 AC: 36310 AN: 152210 Hom.: 4552 Cov.: 32 AF XY: 0.235 AC XY: 17463 AN XY: 74428

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.231

Alfa AF: 0.262 Hom.: 3939

Bravo AF: 0.252

Asia WGS AF: 0.163 AC: 567 AN: 3478

EpiCase AF: 0.275

EpiControl AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.9
DANN	Benign	0.70

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: rs9268480; hg19: chr6-32363844; COSMIC: COSV66630488; COSMIC: COSV66630488;