6-32405921-G-T

Variant names:

• chr6-32405921-G-T
• rs3806156
• NM_001304561.2:c.80-635C>A

Variant summary

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

The NM_001304561.2(BTNL2):​c.80-635C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,712 control chromosomes in the GnomAD database, including 9,995 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 0.36 (9995 hom., cov: 32)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 73 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 (EAS) allele frequency at 95% confidence interval = 0.442 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.80-635C>A		intron	N/A	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.407-196G>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.80-635C>A		intron	N/A	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000446536.3	TSL:1	c.80-638C>A		intron	N/A	ENSP00000388434.2	F6UPS5
	BTNL2	ENST00000465865.6	TSL:1	n.80-635C>A		intron	N/A	ENSP00000420063.1	F8WDK6

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54842 AN: 151594 Hom.: 9991 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.362 AC: 54868 AN: 151712 Hom.: 9995 Cov.: 32 AF XY: 0.364 AC XY: 26993 AN XY: 74138

African (AFR) AF: 0.321 AC: 13248 AN: 41310

American (AMR) AF: 0.439 AC: 6696 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2362 AN: 5162

South Asian (SAS) AF: 0.425 AC: 2044 AN: 4804

European-Finnish (FIN) AF: 0.367 AC: 3845 AN: 10488

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24228 AN: 67902

Other (OTH) AF: 0.366 AC: 773 AN: 2112

Alfa AF: 0.363 Hom.: 38937

Bravo AF: 0.371

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		-0.39
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: rs3806156; hg19: chr6-32373698;