chr6-32396178-T-C

Variant names:

• chr6-32396178-T-C
• rs2076529
• NM_001304561.2:c.939A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304561.2(BTNL2):​c.939A>G​(p.Val313Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,612,670 control chromosomes in the GnomAD database, including 150,036 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (11991 hom., cov: 31)
  • Exomes 𝑓: 0.43 (138045 hom.)
• Consequence: BTNL2 NM_001304561.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• Publications: 68 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.939A>G	p.Val313Val	synonymous_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-9276T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.939A>G	p.Val313Val	synonymous_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60100 AN: 151884 Hom.: 11991 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.393

GnomAD2 exomes AF: 0.415 AC: 102325 AN: 246668 AF XY: 0.413

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.432 AC: 631154 AN: 1460666 Hom.: 138045 Cov.: 60 AF XY: 0.429 AC XY: 311836 AN XY: 726656

African (AFR) AF: 0.319 AC: 10663 AN: 33478

American (AMR) AF: 0.487 AC: 21755 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 9891 AN: 26136

East Asian (EAS) AF: 0.368 AC: 14608 AN: 39690

South Asian (SAS) AF: 0.388 AC: 33470 AN: 86244

European-Finnish (FIN) AF: 0.456 AC: 23885 AN: 52346

Middle Eastern (MID) AF: 0.333 AC: 1920 AN: 5768

European-Non Finnish (NFE) AF: 0.441 AC: 490339 AN: 1111924

Other (OTH) AF: 0.408 AC: 24623 AN: 60374

GnomAD4 genome AF: 0.396 AC: 60119 AN: 152004 Hom.: 11991 Cov.: 31 AF XY: 0.397 AC XY: 29479 AN XY: 74290

African (AFR) AF: 0.331 AC: 13737 AN: 41450

American (AMR) AF: 0.434 AC: 6636 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1548 AN: 5154

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4824

European-Finnish (FIN) AF: 0.456 AC: 4813 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28694 AN: 67964

Other (OTH) AF: 0.387 AC: 816 AN: 2110

Alfa AF: 0.409 Hom.: 49197

Bravo AF: 0.396

Asia WGS AF: 0.318 AC: 1107 AN: 3478

EpiCase AF: 0.409

EpiControl AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		-3.2
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: rs2076529; hg19: chr6-32363955; COSMIC: COSV66630970; COSMIC: COSV66630970;