6-32394044-C-T

Variant names:

• chr6-32394044-C-T
• rs3129953
• NM_001304561.2:c.1374G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304561.2(BTNL2):​c.1374G>A​(p.Thr458Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,549,740 control chromosomes in the GnomAD database, including 18,055 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 (1292 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16763 hom.)
• Consequence: BTNL2 NM_001304561.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 36 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.546 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 7 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-11410C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 7 of 8	5	NM_001304561.2	ENSP00000390613.3
TSBP1-AS1	ENST00000642577.1	n.708+3291C>T		intron_variant	Intron 3 of 5
TSBP1-AS1	ENST00000645134.1	n.627+3291C>T		intron_variant	Intron 2 of 4
TSBP1-AS1	ENST00000645167.1	n.124-12073C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18876 AN: 152068 Hom.: 1293 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.101 AC: 14956 AN: 148536 AF XY: 0.0977

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0619

Gnomad ASJ exome AF: 0.0897

Gnomad EAS exome AF: 0.0563

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.145 AC: 202422 AN: 1397554 Hom.: 16763 Cov.: 33 AF XY: 0.141 AC XY: 96868 AN XY: 689340

African (AFR) AF: 0.116 AC: 3660 AN: 31584

American (AMR) AF: 0.0650 AC: 2319 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 2387 AN: 25178

East Asian (EAS) AF: 0.0402 AC: 1436 AN: 35714

South Asian (SAS) AF: 0.0192 AC: 1520 AN: 79218

European-Finnish (FIN) AF: 0.139 AC: 6704 AN: 48072

Middle Eastern (MID) AF: 0.0537 AC: 306 AN: 5698

European-Non Finnish (NFE) AF: 0.164 AC: 176479 AN: 1078448

Other (OTH) AF: 0.131 AC: 7611 AN: 57958

GnomAD4 genome AF: 0.124 AC: 18884 AN: 152186 Hom.: 1292 Cov.: 32 AF XY: 0.118 AC XY: 8764 AN XY: 74408

African (AFR) AF: 0.116 AC: 4834 AN: 41514

American (AMR) AF: 0.0731 AC: 1117 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 329 AN: 3468

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5180

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10600

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

European-Non Finnish (NFE) AF: 0.154 AC: 10452 AN: 67992

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.144 Hom.: 5607

Bravo AF: 0.119

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3129953; hg19: chr6-32361821;