6-32402810-G-C

Variant names:

• chr6-32402810-G-C
• rs9461741
• NM_001304561.2:c.709+125C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.709+125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,017,408 control chromosomes in the GnomAD database, including 590 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 0.037 (169 hom., cov: 32)
  • Exomes 𝑓: 0.020 (421 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.709+125C>G		intron_variant	Intron 3 of 7	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-2644G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.709+125C>G		intron_variant	Intron 3 of 7	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5612 AN: 152136 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0198 AC: 17117 AN: 865154 Hom.: 421 AF XY: 0.0198 AC XY: 8520 AN XY: 431046

Gnomad4 AFR exome AF: 0.0804

Gnomad4 AMR exome AF: 0.0482

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00122

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.00290

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.0369 AC: 5615 AN: 152254 Hom.: 169 Cov.: 32 AF XY: 0.0349 AC XY: 2598 AN XY: 74448

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.00183 Hom.: 0

Bravo AF: 0.0438

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.66

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: rs9461741; hg19: chr6-32370587;