6-32403842-A-G

Variant names:

• chr6-32403842-A-G
• rs3793126
• NM_001304561.2:c.428-626T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.428-626T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,224 control chromosomes in the GnomAD database, including 4,556 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 0.24 (4549 hom., cov: 32)
  • Exomes 𝑓: 0.25 (7 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 23 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.287 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.428-626T>C		intron	N/A	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-1612A>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.428-626T>C		intron	N/A	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.191+1333T>C		intron	N/A	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.186+1338T>C		intron	N/A	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36260 AN: 151948 Hom.: 4550 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.253 AC: 40 AN: 158 Hom.: 7 Cov.: 0 AF XY: 0.256 AC XY: 21 AN XY: 82

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.271 AC: 38 AN: 140

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.239 AC: 36273 AN: 152066 Hom.: 4549 Cov.: 32 AF XY: 0.235 AC XY: 17440 AN XY: 74346

African (AFR) AF: 0.179 AC: 7443 AN: 41470

American (AMR) AF: 0.295 AC: 4501 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1057 AN: 3472

East Asian (EAS) AF: 0.148 AC: 769 AN: 5182

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4824

European-Finnish (FIN) AF: 0.186 AC: 1963 AN: 10574

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18656 AN: 67956

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.274 Hom.: 6477

Bravo AF: 0.252

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		0.10
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: rs3793126; hg19: chr6-32371619;