NM_001304561.2:c.79+227T>C

Variant names:

• chr6-32406818-A-G
• rs2395158
• NM_001304561.2:c.79+227T>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.79+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 395,194 control chromosomes in the GnomAD database, including 3,564 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 0.12 (1270 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2294 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 13 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 (NFE) allele frequency at 95% confidence interval = 0.151 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.79+227T>C		intron	N/A	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.1108A>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.79+227T>C		intron	N/A	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000446536.3	TSL:1	c.79+227T>C		intron	N/A	ENSP00000388434.2	F6UPS5
	BTNL2	ENST00000465865.6	TSL:1	n.79+227T>C		intron	N/A	ENSP00000420063.1	F8WDK6

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18714 AN: 152042 Hom.: 1271 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.120 AC: 29153 AN: 243034 Hom.: 2294 Cov.: 0 AF XY: 0.118 AC XY: 14692 AN XY: 124672

African (AFR) AF: 0.116 AC: 1061 AN: 9186

American (AMR) AF: 0.0705 AC: 853 AN: 12092

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 800 AN: 8376

East Asian (EAS) AF: 0.0335 AC: 716 AN: 21388

South Asian (SAS) AF: 0.0159 AC: 213 AN: 13376

European-Finnish (FIN) AF: 0.139 AC: 2082 AN: 14972

Middle Eastern (MID) AF: 0.0498 AC: 58 AN: 1164

European-Non Finnish (NFE) AF: 0.147 AC: 21573 AN: 146986

Other (OTH) AF: 0.116 AC: 1797 AN: 15494

GnomAD4 genome AF: 0.123 AC: 18720 AN: 152160 Hom.: 1270 Cov.: 32 AF XY: 0.117 AC XY: 8681 AN XY: 74388

African (AFR) AF: 0.114 AC: 4723 AN: 41514

American (AMR) AF: 0.0732 AC: 1119 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3468

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5174

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4830

European-Finnish (FIN) AF: 0.141 AC: 1489 AN: 10590

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10448 AN: 67968

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.142 Hom.: 3435

Bravo AF: 0.118

Asia WGS AF: 0.0480 AC: 167 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	1.6
DANN	Benign	0.81
PhyloP100		-0.78
PromoterAI		-0.0093	Neutral
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: rs2395158; hg19: chr6-32374595;