NM_001304561.2:c.79+182C>T

Variant names:

• chr6-32406863-G-A
• rs3763308
• NM_001304561.2:c.79+182C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.79+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 548,702 control chromosomes in the GnomAD database, including 1,026 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 0.066 (403 hom., cov: 32)
  • Exomes 𝑓: 0.049 (623 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.79+182C>T		intron	N/A	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.1153G>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.79+182C>T		intron	N/A	ENSP00000390613.3
	BTNL2	ENST00000446536.3	TSL:1	c.79+182C>T		intron	N/A	ENSP00000388434.2
	BTNL2	ENST00000465865.6	TSL:1	n.79+182C>T		intron	N/A	ENSP00000420063.1

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9987 AN: 152076 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0487 AC: 19293 AN: 396508 Hom.: 623 Cov.: 4 AF XY: 0.0485 AC XY: 10100 AN XY: 208192

African (AFR) AF: 0.107 AC: 1357 AN: 12634

American (AMR) AF: 0.0885 AC: 1799 AN: 20332

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 135 AN: 11890

East Asian (EAS) AF: 0.0354 AC: 1106 AN: 31232

South Asian (SAS) AF: 0.0543 AC: 1648 AN: 30326

European-Finnish (FIN) AF: 0.0680 AC: 1968 AN: 28956

Middle Eastern (MID) AF: 0.0517 AC: 106 AN: 2050

European-Non Finnish (NFE) AF: 0.0425 AC: 10026 AN: 235910

Other (OTH) AF: 0.0495 AC: 1148 AN: 23178

GnomAD4 genome AF: 0.0656 AC: 9988 AN: 152194 Hom.: 403 Cov.: 32 AF XY: 0.0659 AC XY: 4901 AN XY: 74424

African (AFR) AF: 0.111 AC: 4608 AN: 41524

American (AMR) AF: 0.0726 AC: 1111 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.0265 AC: 137 AN: 5170

South Asian (SAS) AF: 0.0502 AC: 242 AN: 4822

European-Finnish (FIN) AF: 0.0698 AC: 740 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2907 AN: 67988

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0489 Hom.: 787

Bravo AF: 0.0681

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.33
PhyloP100		0.24
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	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: rs3763308; hg19: chr6-32374640;