5-180911425-C-G

Variant names:

• chr5-180911425-C-G
• rs766111997
• NM_001040462.3:c.484C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040462.3(BTNL8):​c.484C>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R162W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTNL8 NM_001040462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.10
• Publications: 0 publications found

Genes affected

BTNL8 (HGNC:26131): (butyrophilin like 8) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08379638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040462.3. 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
	BTNL8	NM_001040462.3	MANE Select	c.484C>G	p.Arg162Gly	missense	Exon 3 of 8	NP_001035552.1	Q6UX41-1
	BTNL8	NM_001159707.2		c.136C>G	p.Arg46Gly	missense	Exon 2 of 7	NP_001153179.1	Q6UX41-6
	BTNL8	NM_001159709.2		c.109C>G	p.Arg37Gly	missense	Exon 3 of 8	NP_001153181.1	Q6UX41-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.484C>G	p.Arg162Gly	missense	Exon 3 of 8	ENSP00000342197.4	Q6UX41-1
	BTNL8	ENST00000511704.5	TSL:1	c.136C>G	p.Arg46Gly	missense	Exon 2 of 7	ENSP00000425207.1	Q6UX41-6
	BTNL8	ENST00000231229.8	TSL:1	c.484C>G	p.Arg162Gly	missense	Exon 3 of 8	ENSP00000231229.4	Q6UX41-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.6
DANN	Benign	0.91
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.1
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.069
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.17	B
Vest4		0.17
MutPred		0.47		Gain of ubiquitination at K166 (P = 0.0418)
MVP		0.13
MPC		0.21
ClinPred		0.18	T
GERP RS		-7.7
Varity_R		0.082
gMVP		0.098
Mutation Taster		=100/0	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: rs766111997; hg19: chr5-180338425;