chr6-32396267-G-A

Variant names:

• chr6-32396267-G-A
• rs36110770
• NM_001304561.2:c.850C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001304561.2(BTNL2):​c.850C>T​(p.Arg284*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,612,990 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0053 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: BTNL2 NM_001304561.2 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• Publications: 4 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 -10 ACMG points.

• BP6: Variant 6-32396267-G-A is Benign according to our data. Variant chr6-32396267-G-A is described in ClinVar as Benign. ClinVar VariationId is 3341585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00531 (809/152234) while in subpopulation AFR AF = 0.0184 (764/41546). 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 32. 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.850C>T	p.Arg284*	stop_gained	Exon 5 of 8	NP_001291490.1
	TSBP1-AS1	NR_136245.1		n.303-9187G>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.850C>T	p.Arg284*	stop_gained	Exon 5 of 8	ENSP00000390613.3
	BTNL2	ENST00000465865.6	TSL:1	n.*125C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000420063.1
	BTNL2	ENST00000544175.3	TSL:1	n.*111C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000443364.2

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 804 AN: 152116 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.00336

GnomAD2 exomes AF: 0.00146 AC: 360 AN: 246506 AF XY: 0.00101

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000633

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000540 AC: 789 AN: 1460756 Hom.: 4 Cov.: 33 AF XY: 0.000469 AC XY: 341 AN XY: 726690

African (AFR) AF: 0.0175 AC: 585 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52324

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111992

Other (OTH) AF: 0.00131 AC: 79 AN: 60386

GnomAD4 genome AF: 0.00531 AC: 809 AN: 152234 Hom.: 9 Cov.: 32 AF XY: 0.00494 AC XY: 368 AN XY: 74442

African (AFR) AF: 0.0184 AC: 764 AN: 41546

American (AMR) AF: 0.00150 AC: 23 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68010

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00124 Hom.: 4

Bravo AF: 0.00605

ESP6500AA AF: 0.0179 AC: 54

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00177 AC: 210

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BTNL2: BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	57
DANN	Uncertain	1.0
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.23	N
PhyloP100		1.4
Vest4		0.88
GERP RS		4.3
Mutation Taster		=174/26	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs36110770; hg19: chr6-32364044;