rs28362683

chr6-32405186-G-A

Variant summary

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

The NM_001304561.2(BTNL2):c.180C>T(p.His60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,612,882 control chromosomes in the GnomAD database, including 7,047 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 0.10 (965 hom., cov: 32)
  • Exomes 𝑓: 0.080 (6082 hom.)
• Consequence: BTNL2 NM_001304561.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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=-0.52).
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.180C>T	p.His60=	synonymous_variant	2/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-268G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.180C>T	p.His60=	synonymous_variant	2/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.752-268G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15878 AN: 152004 Hom.: 963 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.115 AC: 28365 AN: 246560 Hom.: 2214 AF XY: 0.109 AC XY: 14674 AN XY: 134396

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.0353

Gnomad EAS exome AF: 0.203

Gnomad SAS exome AF: 0.0877

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.0766

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0798 AC: 116523 AN: 1460760 Hom.: 6082 Cov.: 31 AF XY: 0.0797 AC XY: 57894 AN XY: 726698

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.0356

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.0857

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.104 AC: 15888 AN: 152122 Hom.: 965 Cov.: 32 AF XY: 0.109 AC XY: 8115 AN XY: 74352

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0335

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0823 Hom.: 599

Bravo AF: 0.102

Asia WGS AF: 0.140 AC: 486 AN: 3478

EpiCase AF: 0.0701

EpiControl AF: 0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.4
Dann	Benign	0.31

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: rs28362683; hg19: chr6-32372963; COSMIC: COSV66631572;