rs28366191

Variant names:

• chr6-32396413-A-G
• rs28366191
• NM_001304561.2:c.731-27T>C

Variant summary

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

The NM_001304561.2(BTNL2):​c.731-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,581,338 control chromosomes in the GnomAD database, including 4,117 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 0.064 (413 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3704 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.731-27T>C		intron_variant	Intron 4 of 7	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-9041A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.731-27T>C		intron_variant	Intron 4 of 7	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9713 AN: 152138 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0785

GnomAD2 exomes AF: 0.0535 AC: 12327 AN: 230428 AF XY: 0.0534

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.0609

Gnomad ASJ exome AF: 0.0640

Gnomad EAS exome AF: 0.0611

Gnomad FIN exome AF: 0.00752

Gnomad NFE exome AF: 0.0596

Gnomad OTH exome AF: 0.0663

GnomAD4 exome AF: 0.0666 AC: 95150 AN: 1429082 Hom.: 3704 Cov.: 27 AF XY: 0.0649 AC XY: 46187 AN XY: 711988

African (AFR) AF: 0.0683 AC: 2243 AN: 32850

American (AMR) AF: 0.0654 AC: 2865 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 1715 AN: 25822

East Asian (EAS) AF: 0.0249 AC: 981 AN: 39468

South Asian (SAS) AF: 0.0342 AC: 2895 AN: 84634

European-Finnish (FIN) AF: 0.00862 AC: 426 AN: 49398

Middle Eastern (MID) AF: 0.0280 AC: 160 AN: 5706

European-Non Finnish (NFE) AF: 0.0735 AC: 79981 AN: 1087990

Other (OTH) AF: 0.0654 AC: 3884 AN: 59376

GnomAD4 genome AF: 0.0638 AC: 9717 AN: 152256 Hom.: 413 Cov.: 32 AF XY: 0.0604 AC XY: 4498 AN XY: 74440

African (AFR) AF: 0.0756 AC: 3142 AN: 41540

American (AMR) AF: 0.0868 AC: 1328 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3472

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5182

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4824

European-Finnish (FIN) AF: 0.00604 AC: 64 AN: 10604

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4365 AN: 68022

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0610 Hom.: 792

Bravo AF: 0.0729

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		-0.20
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: rs28366191; hg19: chr6-32364190; COSMIC: COSV66631239; COSMIC: COSV66631239;