rs9268480

Variant names:

• chr6-32396067-C-T
• rs9268480
• NM_001304561.2:c.1050G>A

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.1050G>A​(p.Gln350Gln) 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
• Publications: 72 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=-0.7).
• 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.1050G>A	p.Gln350Gln	synonymous	Exon 5 of 8	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-9387C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.1050G>A	p.Gln350Gln	synonymous	Exon 5 of 8	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000465865.6	TSL:1	n.*325G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000420063.1	F8WDK6
	BTNL2	ENST00000544175.3	TSL:1	n.*311G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000443364.2	Q9UIR0-8

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

GnomAD2 exomes AF: 0.258 AC: 63383 AN: 245970 AF XY: 0.255

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 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

African (AFR) AF: 0.168 AC: 5615 AN: 33476

American (AMR) AF: 0.338 AC: 15128 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7742 AN: 26128

East Asian (EAS) AF: 0.132 AC: 5220 AN: 39690

South Asian (SAS) AF: 0.216 AC: 18595 AN: 86248

European-Finnish (FIN) AF: 0.194 AC: 10156 AN: 52302

Middle Eastern (MID) AF: 0.226 AC: 1305 AN: 5766

European-Non Finnish (NFE) AF: 0.293 AC: 325438 AN: 1111652

Other (OTH) AF: 0.265 AC: 16021 AN: 60378

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

African (AFR) AF: 0.180 AC: 7459 AN: 41528

American (AMR) AF: 0.294 AC: 4496 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1057 AN: 3472

East Asian (EAS) AF: 0.148 AC: 770 AN: 5186

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4824

European-Finnish (FIN) AF: 0.186 AC: 1973 AN: 10598

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18676 AN: 68016

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.259 Hom.: 12063

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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