6-32402810-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.709+125C>G		intron	N/A	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-2644G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.709+125C>G		intron	N/A	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000465865.6	TSL:1	n.192-1005C>G		intron	N/A	ENSP00000420063.1	F8WDK6
	BTNL2	ENST00000544175.3	TSL:1	n.187-1005C>G		intron	N/A	ENSP00000443364.2	Q9UIR0-8

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

African (AFR) AF: 0.0804 AC: 1625 AN: 20222

American (AMR) AF: 0.0482 AC: 992 AN: 20580

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2065 AN: 16460

East Asian (EAS) AF: 0.00122 AC: 40 AN: 32780

South Asian (SAS) AF: 0.0143 AC: 741 AN: 51994

European-Finnish (FIN) AF: 0.00290 AC: 117 AN: 40292

Middle Eastern (MID) AF: 0.110 AC: 424 AN: 3844

European-Non Finnish (NFE) AF: 0.0154 AC: 9825 AN: 639476

Other (OTH) AF: 0.0326 AC: 1288 AN: 39506

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

African (AFR) AF: 0.0752 AC: 3123 AN: 41526

American (AMR) AF: 0.0462 AC: 707 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3466

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4816

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1092 AN: 68032

Other (OTH) AF: 0.0635 AC: 134 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.66
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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: rs9461741; hg19: chr6-32370587;