chr6-32394968-G-A

Variant names:

• chr6-32394968-G-A
• rs28362678
• NM_001304561.2:c.1136C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.1136C>T​(p.Pro379Leu) variant causes a missense change. The variant allele was found at a frequency of 0.153 in 1,610,580 control chromosomes in the GnomAD database, including 20,132 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.15 (1814 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18318 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 34 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014532506).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.1136C>T	p.Pro379Leu	missense_variant	Exon 6 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-10486G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.1136C>T	p.Pro379Leu	missense_variant	Exon 6 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22977 AN: 151924 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.153 AC: 38173 AN: 249352 AF XY: 0.154

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.0787

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.153 AC: 223713 AN: 1458538 Hom.: 18318 Cov.: 33 AF XY: 0.154 AC XY: 111459 AN XY: 725386

African (AFR) AF: 0.133 AC: 4435 AN: 33418

American (AMR) AF: 0.145 AC: 6459 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 2100 AN: 26034

East Asian (EAS) AF: 0.235 AC: 9301 AN: 39528

South Asian (SAS) AF: 0.170 AC: 14568 AN: 85686

European-Finnish (FIN) AF: 0.261 AC: 13927 AN: 53294

Middle Eastern (MID) AF: 0.105 AC: 606 AN: 5760

European-Non Finnish (NFE) AF: 0.148 AC: 163862 AN: 1110028

Other (OTH) AF: 0.140 AC: 8455 AN: 60254

GnomAD4 genome AF: 0.151 AC: 22977 AN: 152042 Hom.: 1814 Cov.: 32 AF XY: 0.157 AC XY: 11642 AN XY: 74314

African (AFR) AF: 0.133 AC: 5527 AN: 41502

American (AMR) AF: 0.138 AC: 2109 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 274 AN: 3466

East Asian (EAS) AF: 0.151 AC: 781 AN: 5160

South Asian (SAS) AF: 0.184 AC: 883 AN: 4794

European-Finnish (FIN) AF: 0.269 AC: 2839 AN: 10550

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9996 AN: 67976

Other (OTH) AF: 0.151 AC: 318 AN: 2106

Alfa AF: 0.143 Hom.: 3563

Bravo AF: 0.137

TwinsUK AF: 0.122 AC: 451

ALSPAC AF: 0.129 AC: 498

ESP6500AA AF: 0.125 AC: 551

ESP6500EA AF: 0.144 AC: 1241

ExAC AF: 0.155 AC: 18765

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.8
DANN	Benign	0.73
DEOGEN2	Benign	0.0028	T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00036	N
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.8	.;N;.
PhyloP100		3.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.4	.;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	.;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.085
MPC		0.37
ClinPred		0.0066	T
GERP RS		2.6
Varity_R		0.043
gMVP		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28362678; hg19: chr6-32362745; COSMIC: COSV66630186; COSMIC: COSV66630186;