rs4248166

Variant names:

• chr6-32398644-T-C
• rs4248166
• NM_001304561.2:c.731-2258A>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.731-2258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,882 control chromosomes in the GnomAD database, including 2,768 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 0.18 (2768 hom., cov: 32)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 51 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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.731-2258A>G		intron	N/A	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-6810T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.731-2258A>G		intron	N/A	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000465865.6	TSL:1	n.*6-2258A>G		intron	N/A	ENSP00000420063.1	F8WDK6
	BTNL2	ENST00000544175.3	TSL:1	n.208-2258A>G		intron	N/A	ENSP00000443364.2	Q9UIR0-8

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27570 AN: 151764 Hom.: 2764 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0543

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.182 AC: 27590 AN: 151882 Hom.: 2768 Cov.: 32 AF XY: 0.189 AC XY: 14051 AN XY: 74172

African (AFR) AF: 0.157 AC: 6511 AN: 41514

American (AMR) AF: 0.190 AC: 2893 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0543 AC: 188 AN: 3462

East Asian (EAS) AF: 0.218 AC: 1104 AN: 5058

South Asian (SAS) AF: 0.122 AC: 575 AN: 4732

European-Finnish (FIN) AF: 0.376 AC: 3966 AN: 10552

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11731 AN: 68002

Other (OTH) AF: 0.175 AC: 369 AN: 2104

Alfa AF: 0.167 Hom.: 8721

Bravo AF: 0.166

Asia WGS AF: 0.168 AC: 580 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.28
PhyloP100		-0.36
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: rs4248166; hg19: chr6-32366421;