6-32394968-G-T

Position:

• chr6-32394968-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304561.2(BTNL2):​c.1136C>A​(p.Pro379Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P379L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070762604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.1136C>A	p.Pro379Gln	missense_variant	6/8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-10486G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.1136C>A	p.Pro379Gln	missense_variant	6/8	5	NM_001304561.2	ENSP00000390613	P1
TSBP1-AS1	ENST00000645134.1	n.627+4215G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461000 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726690

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.0038	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.32	.;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.76	.;P;.
Vest4		0.28
MutPred		0.33		Gain of catalytic residue at P379 (P = 0.0626);Gain of catalytic residue at P379 (P = 0.0626);.;
MVP		0.072
MPC		0.34
ClinPred		0.27	T
GERP RS		2.6
Varity_R		0.039
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28362678; hg19: chr6-32362745;