6-32396120-G-A

Variant names:

• chr6-32396120-G-A
• rs1776433287
• NM_001304561.2:c.997C>T

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.997C>T​(p.Pro333Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. P333T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• 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 (MetaRNN=0.06284505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.997C>T	p.Pro333Ser	missense_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-9334G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.997C>T	p.Pro333Ser	missense_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.70	.;N;.
PhyloP100		-0.36
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.66	.;N;N
REVEL	Benign	0.015
Sift	Uncertain	0.027	.;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.24	.;B;.
Vest4		0.051
MutPred		0.38		Gain of phosphorylation at P333 (P = 0.0551);Gain of phosphorylation at P333 (P = 0.0551);.;
MVP		0.58
MPC		0.43
ClinPred		0.11	T
GERP RS		-1.4
Varity_R		0.045
gMVP		0.45
Mutation Taster		=98/2	polymorphism

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: rs1776433287; hg19: chr6-32363897;