6-32395939-A-G

Variant names:

• chr6-32395939-A-G
• rs35125315
• NM_001304561.2:c.1078+100T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001304561.2(BTNL2):​c.1078+100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 943,050 control chromosomes in the GnomAD database, including 10 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 0.0053 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958
• Publications: 0 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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00532 (810/152364) while in subpopulation AFR AF = 0.0184 (765/41582). AF 95% confidence interval is 0.0173. There are 9 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.1078+100T>C		intron	N/A	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-9515A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.1078+100T>C		intron	N/A	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.*349+104T>C		intron	N/A	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.*339+100T>C		intron	N/A	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 805 AN: 152246 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000554 AC: 438 AN: 790686 Hom.: 1 AF XY: 0.000472 AC XY: 189 AN XY: 400298

African (AFR) AF: 0.0162 AC: 318 AN: 19680

American (AMR) AF: 0.00181 AC: 42 AN: 23156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16006

East Asian (EAS) AF: 0.00 AC: 0 AN: 35158

South Asian (SAS) AF: 0.000112 AC: 6 AN: 53572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39942

Middle Eastern (MID) AF: 0.00122 AC: 4 AN: 3266

European-Non Finnish (NFE) AF: 0.0000267 AC: 15 AN: 562610

Other (OTH) AF: 0.00142 AC: 53 AN: 37296

GnomAD4 genome AF: 0.00532 AC: 810 AN: 152364 Hom.: 9 Cov.: 33 AF XY: 0.00494 AC XY: 368 AN XY: 74514

African (AFR) AF: 0.0184 AC: 765 AN: 41582

American (AMR) AF: 0.00150 AC: 23 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00374 Hom.: 1

Bravo AF: 0.00605

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		0.96
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: rs35125315; hg19: chr6-32363716;