chr6-32403082-C-A

Variant names:

• chr6-32403082-C-A
• rs9461742
• NM_001304561.2:c.562G>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.562G>T​(p.Val188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 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. V188M) has been classified as 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: -11.2
• Publications: 2 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=0.039928347).

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.562G>T	p.Val188Leu	missense	Exon 3 of 8	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-2372C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.562G>T	p.Val188Leu	missense	Exon 3 of 8	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000465865.6	TSL:1	n.192-1277G>T		intron	N/A	ENSP00000420063.1	F8WDK6
	BTNL2	ENST00000544175.3	TSL:1	n.187-1277G>T		intron	N/A	ENSP00000443364.2	Q9UIR0-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246546 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460638 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726644

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111918

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000848 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.0010
DANN	Benign	0.75
DEOGEN2	Benign	0.013	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0077	N
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.21	N
PhyloP100		-11
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.035
MutPred		0.20		Loss of ubiquitination at K184 (P = 0.1741)
MVP		0.30
MPC		0.36
ClinPred		0.047	T
GERP RS		-8.9
Varity_R		0.021
gMVP		0.099
Mutation Taster		=99/1	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: rs9461742; hg19: chr6-32370859;