6-32394902-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001304561.2(BTNL2):c.1202C>T(p.Thr401Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,614,194 control chromosomes in the GnomAD database, including 13 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (4 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.706

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036521256).
• BP6: Variant 6-32394902-G-A is Benign according to our data. Variant chr6-32394902-G-A is described in ClinVar as [Benign]. Clinvar id is 791141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00533 (812/152324) while in subpopulation AFR AF= 0.0184 (765/41560). AF 95% confidence interval is 0.0173. There are 9 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.1202C>T	p.Thr401Met	missense_variant	6/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-10552G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.1202C>T	p.Thr401Met	missense_variant	6/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.627+4149G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 807 AN: 152206 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00152 AC: 382 AN: 251432 Hom.: 3 AF XY: 0.00105 AC XY: 143 AN XY: 135892

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000546 AC: 798 AN: 1461870 Hom.: 4 Cov.: 33 AF XY: 0.000474 AC XY: 345 AN XY: 727234

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000351

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00533 AC: 812 AN: 152324 Hom.: 9 Cov.: 32 AF XY: 0.00497 AC XY: 370 AN XY: 74490

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00119 Hom.: 2

Bravo AF: 0.00608

ESP6500AA AF: 0.0186 AC: 82

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00185 AC: 224

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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

Mar 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	10
Dann	Benign	0.96
DEOGEN2	Benign	0.021	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.33	T
Sift4G	Uncertain	0.034	D;D;T
Polyphen		0.031	.;B;.
Vest4		0.15
MVP		0.49
MPC		0.42
ClinPred		0.0047	T
GERP RS		-1.1
Varity_R		0.020
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs149545886; hg19: chr6-32362679;