rs28362683

Variant names:

• chr6-32405186-G-A
• rs28362683
• NM_001304561.2:c.180C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304561.2(BTNL2):​c.180C>T​(p.His60His) 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.180C>T	p.His60His	synonymous	Exon 2 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-268G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.180C>T	p.His60His	synonymous	Exon 2 of 8	ENSP00000390613.3
	BTNL2	ENST00000446536.3	TSL:1	c.177C>T	p.His59His	synonymous	Exon 2 of 2	ENSP00000388434.2
	BTNL2	ENST00000465865.6	TSL:1	n.180C>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000420063.1

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

GnomAD2 exomes AF: 0.115 AC: 28365 AN: 246560 AF XY: 0.109

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 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

African (AFR) AF: 0.123 AC: 4128 AN: 33478

American (AMR) AF: 0.192 AC: 8594 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0356 AC: 931 AN: 26136

East Asian (EAS) AF: 0.190 AC: 7534 AN: 39700

South Asian (SAS) AF: 0.0857 AC: 7390 AN: 86258

European-Finnish (FIN) AF: 0.169 AC: 8866 AN: 52312

Middle Eastern (MID) AF: 0.0596 AC: 344 AN: 5768

European-Non Finnish (NFE) AF: 0.0661 AC: 73482 AN: 1112000

Other (OTH) AF: 0.0870 AC: 5254 AN: 60384

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

African (AFR) AF: 0.119 AC: 4942 AN: 41496

American (AMR) AF: 0.133 AC: 2026 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 116 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1022 AN: 5178

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4814

European-Finnish (FIN) AF: 0.177 AC: 1874 AN: 10570

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5163 AN: 68010

Other (OTH) AF: 0.115 AC: 243 AN: 2106

Alfa AF: 0.0858 Hom.: 848

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.4
DANN	Benign	0.31
PhyloP100		1.4
Mutation Taster		=280/20	polymorphism (auto)

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

Other links and lift over

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