chr6-32395997-G-A

Variant names:

• chr6-32395997-G-A
• rs17202456
• NM_001304561.2:c.1078+42C>T

Variant summary

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

The NM_001304561.2(BTNL2):​c.1078+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,469,812 control chromosomes in the GnomAD database, including 15,162 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 0.14 (1609 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13553 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 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.1078+42C>T		intron	N/A	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-9457G>A		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+42C>T		intron	N/A	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.*349+46C>T		intron	N/A	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.*339+42C>T		intron	N/A	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21203 AN: 152078 Hom.: 1609 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.134 AC: 27924 AN: 208808 AF XY: 0.132

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.0468

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.138 AC: 181768 AN: 1317616 Hom.: 13553 Cov.: 20 AF XY: 0.136 AC XY: 88587 AN XY: 652094

African (AFR) AF: 0.130 AC: 3976 AN: 30610

American (AMR) AF: 0.135 AC: 5360 AN: 39620

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 734 AN: 22302

East Asian (EAS) AF: 0.0747 AC: 2889 AN: 38662

South Asian (SAS) AF: 0.0891 AC: 6732 AN: 75528

European-Finnish (FIN) AF: 0.261 AC: 13101 AN: 50118

Middle Eastern (MID) AF: 0.0668 AC: 355 AN: 5314

European-Non Finnish (NFE) AF: 0.142 AC: 141931 AN: 1000312

Other (OTH) AF: 0.121 AC: 6690 AN: 55150

GnomAD4 genome AF: 0.139 AC: 21206 AN: 152196 Hom.: 1609 Cov.: 32 AF XY: 0.143 AC XY: 10629 AN XY: 74404

African (AFR) AF: 0.131 AC: 5446 AN: 41520

American (AMR) AF: 0.129 AC: 1972 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5186

South Asian (SAS) AF: 0.0856 AC: 413 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2858 AN: 10582

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9641 AN: 68014

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.134 Hom.: 2354

Bravo AF: 0.127

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.62
PhyloP100		0.34
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: rs17202456; hg19: chr6-32363774; COSMIC: COSV66632212; COSMIC: COSV66632212;