6-32399482-T-G

Position:

• chr6-32399482-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.730+2303A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,132 control chromosomes in the GnomAD database, including 2,691 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 (2691 hom., cov: 32)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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]

BTNL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.730+2303A>C		intron_variant		ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-5972T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.730+2303A>C		intron_variant		5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27051 AN: 152014 Hom.: 2688 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.178 AC: 27063 AN: 152132 Hom.: 2691 Cov.: 32 AF XY: 0.186 AC XY: 13820 AN XY: 74376

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.174

Alfa AF: 0.165 Hom.: 1904

Bravo AF: 0.162

Asia WGS AF: 0.171 AC: 592 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294884; hg19: chr6-32367259;