chr6-32406818-A-T

Variant names:

• chr6-32406818-A-T
• rs2395158
• NM_001304561.2:c.79+227T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304561.2(BTNL2):​c.79+227T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 243,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.79+227T>A		intron_variant	Intron 1 of 7	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.1108A>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.79+227T>A		intron_variant	Intron 1 of 7	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 1 AN: 243392 Hom.: 0 Cov.: 0 AF XY: 0.00000801 AC XY: 1 AN XY: 124870

African (AFR) AF: 0.00 AC: 0 AN: 9200

American (AMR) AF: 0.00 AC: 0 AN: 12106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8382

East Asian (EAS) AF: 0.00 AC: 0 AN: 21398

South Asian (SAS) AF: 0.00 AC: 0 AN: 13380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1164

European-Non Finnish (NFE) AF: 0.00000679 AC: 1 AN: 147242

Other (OTH) AF: 0.00 AC: 0 AN: 15522

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.78
PromoterAI		-0.018	Neutral

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: rs2395158; hg19: chr6-32374595;