6-32403082-C-T

Variant names:

• chr6-32403082-C-T
• rs9461742
• NM_001304561.2:c.562G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001304561.2(BTNL2):​c.562G>A​(p.Val188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,612,898 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (4 hom.)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -11.2
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008282185).
• BP6: Variant 6-32403082-C-T is Benign according to our data. Variant chr6-32403082-C-T is described in ClinVar as Benign. ClinVar VariationId is 768075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.562G>A	p.Val188Met	missense	Exon 3 of 8	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-2372C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.562G>A	p.Val188Met	missense	Exon 3 of 8	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000465865.6	TSL:1	n.192-1277G>A		intron	N/A	ENSP00000420063.1	F8WDK6
	BTNL2	ENST00000544175.3	TSL:1	n.187-1277G>A		intron	N/A	ENSP00000443364.2	Q9UIR0-8

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 570 AN: 152142 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00119 AC: 294 AN: 246546 AF XY: 0.00102

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.000602

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.000531 AC: 775 AN: 1460638 Hom.: 4 Cov.: 34 AF XY: 0.000501 AC XY: 364 AN XY: 726644

African (AFR) AF: 0.0131 AC: 440 AN: 33472

American (AMR) AF: 0.00154 AC: 69 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39688

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52308

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1111918

Other (OTH) AF: 0.00132 AC: 80 AN: 60386

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152260 Hom.: 2 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74460

African (AFR) AF: 0.0120 AC: 497 AN: 41528

American (AMR) AF: 0.00255 AC: 39 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68034

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00140 Hom.: 3

Bravo AF: 0.00445

ESP6500AA AF: 0.0129 AC: 39

ESP6500EA AF: 0.000739 AC: 4

ExAC AF: 0.00121 AC: 143

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0010
DANN	Benign	0.83
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		-11
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.27
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.93	P
Vest4		0.084
MVP		0.35
MPC		0.40
ClinPred		0.019	T
GERP RS		-8.9
Varity_R		0.014
gMVP		0.083
Mutation Taster		=95/5	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: rs9461742; hg19: chr6-32370859;