chr6-32401578-C-T

Variant names:

• chr6-32401578-C-T
• rs3763304
• NM_001304561.2:c.730+207G>A

Variant summary

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

The NM_001304561.2(BTNL2):​c.730+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,058 control chromosomes in the GnomAD database, including 2,711 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 0.18 (2711 hom., cov: 31)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.730+207G>A		intron_variant	Intron 4 of 7	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-3876C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.730+207G>A		intron_variant	Intron 4 of 7	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27100 AN: 151940 Hom.: 2708 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27113 AN: 152058 Hom.: 2711 Cov.: 31 AF XY: 0.186 AC XY: 13856 AN XY: 74312

African (AFR) AF: 0.140 AC: 5807 AN: 41480

American (AMR) AF: 0.189 AC: 2891 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5168

South Asian (SAS) AF: 0.128 AC: 615 AN: 4818

European-Finnish (FIN) AF: 0.377 AC: 3979 AN: 10548

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11886 AN: 67982

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.169 Hom.: 3849

Bravo AF: 0.162

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.30
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3763304; hg19: chr6-32369355;