rs2294881

Variant names:

• chr6-32399827-T-C
• rs2294881
• NM_001304561.2:c.730+1958A>G

Variant summary

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

The NM_001304561.2(BTNL2):​c.730+1958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,160 control chromosomes in the GnomAD database, including 3,203 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 0.20 (3203 hom., cov: 32)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 31 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.730+1958A>G		intron_variant	Intron 4 of 7	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-5627T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.730+1958A>G		intron_variant	Intron 4 of 7	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29769 AN: 152042 Hom.: 3199 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29785 AN: 152160 Hom.: 3203 Cov.: 32 AF XY: 0.205 AC XY: 15282 AN XY: 74368

African (AFR) AF: 0.161 AC: 6672 AN: 41528

American (AMR) AF: 0.200 AC: 3057 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1675 AN: 5180

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3991 AN: 10552

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12271 AN: 68008

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.179 Hom.: 5893

Bravo AF: 0.178

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.40
PhyloP100		-1.9
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: rs2294881; hg19: chr6-32367604;