rs1756725085

Variant names:

• chr5-180899323-C-G
• rs1756725085
• NM_001040462.3:c.13C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-180899323-C-G
• chr5-180899323-C-T

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.13C>G​(p.Leu5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L5F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTNL8 NM_001040462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• 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=0.09807345).

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.13C>G	p.Leu5Val	missense	Exon 1 of 8	NP_001035552.1	Q6UX41-1
	BTNL8	NM_001159707.2		c.13C>G	p.Leu5Val	missense	Exon 1 of 7	NP_001153179.1	Q6UX41-6
	BTNL8	NM_024850.3		c.13C>G	p.Leu5Val	missense	Exon 1 of 8	NP_079126.1	Q6UX41-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.13C>G	p.Leu5Val	missense	Exon 1 of 8	ENSP00000342197.4	Q6UX41-1
	BTNL8	ENST00000511704.5	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 7	ENSP00000425207.1	Q6UX41-6
	BTNL8	ENST00000231229.8	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 8	ENSP00000231229.4	Q6UX41-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.6
DANN	Benign	0.77
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.43
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.023
Sift	Benign	0.042	D
Sift4G	Benign	0.24	T
Polyphen		0.69	P
Vest4		0.20
MutPred		0.41		Gain of catalytic residue at L5 (P = 0.0208)
MVP		0.21
MPC		0.14
ClinPred		0.18	T
GERP RS		-1.1
PromoterAI		0.017	Neutral
Varity_R		0.084
gMVP		0.088
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1756725085; hg19: chr5-180326323;