chr6-32394964-C-T

Variant names:

• chr6-32394964-C-T
• rs28362677
• NM_001304561.2:c.1140G>A

Variant summary

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

The NM_001304561.2(BTNL2):​c.1140G>A​(p.Met380Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,610,748 control chromosomes in the GnomAD database, including 20,129 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 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 (1810 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18319 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 32 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=0.026081413).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.1140G>A	p.Met380Ile	missense	Exon 6 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-10490C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.1140G>A	p.Met380Ile	missense	Exon 6 of 8	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.*411G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.*401G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22975 AN: 151978 Hom.: 1810 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: 38301 AN: 249680 AF XY: 0.154

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.0789

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.153 AC: 223731 AN: 1458652 Hom.: 18319 Cov.: 33 AF XY: 0.154 AC XY: 111479 AN XY: 725472

African (AFR) AF: 0.133 AC: 4438 AN: 33424

American (AMR) AF: 0.145 AC: 6473 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 2099 AN: 26036

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

South Asian (SAS) AF: 0.170 AC: 14608 AN: 85772

European-Finnish (FIN) AF: 0.261 AC: 13933 AN: 53314

Middle Eastern (MID) AF: 0.105 AC: 605 AN: 5758

European-Non Finnish (NFE) AF: 0.148 AC: 163820 AN: 1110010

Other (OTH) AF: 0.140 AC: 8454 AN: 60254

GnomAD4 genome AF: 0.151 AC: 22975 AN: 152096 Hom.: 1810 Cov.: 32 AF XY: 0.157 AC XY: 11643 AN XY: 74354

African (AFR) AF: 0.133 AC: 5526 AN: 41524

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: 5164

South Asian (SAS) AF: 0.184 AC: 884 AN: 4800

European-Finnish (FIN) AF: 0.269 AC: 2844 AN: 10556

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

European-Non Finnish (NFE) AF: 0.147 AC: 9988 AN: 67988

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.142 Hom.: 3565

Bravo AF: 0.137

TwinsUK AF: 0.121 AC: 448

ALSPAC AF: 0.128 AC: 494

ESP6500AA AF: 0.125 AC: 551

ESP6500EA AF: 0.144 AC: 1241

ExAC AF: 0.154 AC: 18762

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.5
DANN	Benign	0.65
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.047	N
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.0050
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.095
Sift	Benign	0.22	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.047
MutPred		0.13		Loss of disorder (P = 0.0591)
MPC		0.40
ClinPred		0.0096	T
GERP RS		3.3
Varity_R		0.27
gMVP		0.28
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28362677; hg19: chr6-32362741; COSMIC: COSV66630182; COSMIC: COSV66630182;