rs564122210

Variant names:

• chr5-180908814-C-A
• rs564122210
• NM_001040462.3:c.278C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-180908814-C-A
• chr5-180908814-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.278C>A​(p.Ala93Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A93V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BTNL8 NM_001040462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=0.09943321).

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.278C>A	p.Ala93Glu	missense	Exon 2 of 8	NP_001035552.1	Q6UX41-1
	BTNL8	NM_024850.3		c.278C>A	p.Ala93Glu	missense	Exon 2 of 8	NP_079126.1	Q6UX41-5
	BTNL8	NM_001159708.2		c.278C>A	p.Ala93Glu	missense	Exon 2 of 7	NP_001153180.1	Q6UX41-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.278C>A	p.Ala93Glu	missense	Exon 2 of 8	ENSP00000342197.4	Q6UX41-1
	BTNL8	ENST00000231229.8	TSL:1	c.278C>A	p.Ala93Glu	missense	Exon 2 of 8	ENSP00000231229.4	Q6UX41-5
	BTNL8	ENST00000508408.5	TSL:1	c.278C>A	p.Ala93Glu	missense	Exon 2 of 7	ENSP00000424585.1	Q6UX41-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251094 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.24
DANN	Benign	0.76
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.4
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.071
Sift	Benign	0.22	T
Sift4G	Benign	0.10	T
Polyphen		0.97	D
Vest4		0.16
MutPred		0.45		Gain of disorder (P = 0.0174)
MVP		0.34
MPC		0.23
ClinPred		0.15	T
GERP RS		-2.0
Varity_R		0.13
gMVP		0.046
Mutation Taster		=98/2	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: rs564122210; hg19: chr5-180335814;