NM_001304561.2:c.1006G>A

Variant names:

• chr6-32396111-C-T
• rs41441651
• NM_001304561.2:c.1006G>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.1006G>A​(p.Asp336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,088 control chromosomes in the GnomAD database, including 1,128 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 0.012 (68 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1060 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 22 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=0.004987538).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 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.1006G>A	p.Asp336Asn	missense	Exon 5 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-9343C>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.1006G>A	p.Asp336Asn	missense	Exon 5 of 8	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.*281G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.*267G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1861 AN: 152196 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0232 AC: 5725 AN: 246562 AF XY: 0.0263

Gnomad AFR exome AF: 0.00132

Gnomad AMR exome AF: 0.00946

Gnomad ASJ exome AF: 0.0498

Gnomad EAS exome AF: 0.0824

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00685

Gnomad OTH exome AF: 0.0216

GnomAD4 exome AF: 0.0155 AC: 22571 AN: 1460774 Hom.: 1060 Cov.: 56 AF XY: 0.0179 AC XY: 12998 AN XY: 726708

African (AFR) AF: 0.00146 AC: 49 AN: 33480

American (AMR) AF: 0.00993 AC: 444 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0489 AC: 1279 AN: 26136

East Asian (EAS) AF: 0.162 AC: 6415 AN: 39700

South Asian (SAS) AF: 0.0828 AC: 7145 AN: 86248

European-Finnish (FIN) AF: 0.000268 AC: 14 AN: 52326

Middle Eastern (MID) AF: 0.0383 AC: 221 AN: 5766

European-Non Finnish (NFE) AF: 0.00524 AC: 5828 AN: 1112008

Other (OTH) AF: 0.0195 AC: 1176 AN: 60386

GnomAD4 genome AF: 0.0122 AC: 1859 AN: 152314 Hom.: 68 Cov.: 32 AF XY: 0.0142 AC XY: 1056 AN XY: 74470

African (AFR) AF: 0.00226 AC: 94 AN: 41562

American (AMR) AF: 0.00928 AC: 142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.109 AC: 566 AN: 5178

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00551 AC: 375 AN: 68036

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0107 Hom.: 60

Bravo AF: 0.00990

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00132 AC: 4

ESP6500EA AF: 0.00904 AC: 49

ExAC AF: 0.0237 AC: 2811

Asia WGS AF: 0.0810 AC: 282 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.054	N
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.24	N
PhyloP100		-0.11
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.016
Sift	Benign	0.90	T
Sift4G	Benign	0.33	T
Polyphen		0.092	B
Vest4		0.020
MPC		0.41
ClinPred		0.0072	T
GERP RS		2.3
Varity_R		0.094
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs41441651; hg19: chr6-32363888; COSMIC: COSV66630792; COSMIC: COSV66630792;