6-32403082-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001304561.2(BTNL2):c.562G>A(p.Val188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,612,898 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (4 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -11.2

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008282185).
• BP6: Variant 6-32403082-C-T is Benign according to our data. Variant chr6-32403082-C-T is described in ClinVar as [Benign]. Clinvar id is 768075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.562G>A	p.Val188Met	missense_variant	3/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-2372C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.562G>A	p.Val188Met	missense_variant	3/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.628-587C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 570 AN: 152142 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00119 AC: 294 AN: 246546 Hom.: 2 AF XY: 0.00102 AC XY: 137 AN XY: 134398

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.000602

Gnomad SAS exome AF: 0.000527

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.000531 AC: 775 AN: 1460638 Hom.: 4 Cov.: 34 AF XY: 0.000501 AC XY: 364 AN XY: 726644

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.000475

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152260 Hom.: 2 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74460

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00102 Hom.: 1

Bravo AF: 0.00445

ESP6500AA AF: 0.0129 AC: 39

ESP6500EA AF: 0.000739 AC: 4

ExAC AF: 0.00121 AC: 143

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	0.0010
Dann	Benign	0.83
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
MetaRNN	Benign	0.0083	T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.17	T;T
Polyphen		0.93	.;P
Vest4		0.084
MVP		0.35
MPC		0.40
ClinPred		0.019	T
GERP RS		-8.9
Varity_R		0.014
gMVP		0.083

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

Publications

LitVar

Other links and lift over

dbSNP: rs9461742; hg19: chr6-32370859;