6-32407088-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001304561.2(BTNL2):c.36A>G(p.Ala12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,613,022 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (14 hom.)
• Consequence: BTNL2 NM_001304561.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.32

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-32407088-T-C is Benign according to our data. Variant chr6-32407088-T-C is described in ClinVar as [Benign]. Clinvar id is 731754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.36A>G	p.Ala12=	synonymous_variant	1/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.1378T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.36A>G	p.Ala12=	synonymous_variant	1/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.1827T>C		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152198 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00306 AC: 756 AN: 246974 Hom.: 7 AF XY: 0.00343 AC XY: 461 AN XY: 134588

Gnomad AFR exome AF: 0.000459

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.00137

Gnomad SAS exome AF: 0.0117

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00243

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00275 AC: 4018 AN: 1460706 Hom.: 14 Cov.: 30 AF XY: 0.00292 AC XY: 2121 AN XY: 726664

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.00166

Gnomad4 SAS exome AF: 0.00922

Gnomad4 FIN exome AF: 0.000822

Gnomad4 NFE exome AF: 0.00252

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74478

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00166

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	BTNL2: BP4, BP7, BS1, BS2; TSBP1-AS1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.26
Dann	Benign	0.42

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: rs41395046; hg19: chr6-32374865;